138 results on '"Manuela Sironi"'
Search Results
2. Kinetochore proteins and microtubule‐destabilizing factors are fast evolving in eutherian mammals
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Rachele Cagliani, Diego Forni, Mario Clerici, Chiara Pontremoli, Manuela Sironi, and Uberto Pozzoli
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0106 biological sciences ,0301 basic medicine ,Nonsynonymous substitution ,Eutheria ,Kinetochore ,Centromere ,Biology ,Microtubules ,010603 evolutionary biology ,01 natural sciences ,Chromosome segregation ,03 medical and health sciences ,030104 developmental biology ,Meiotic drive ,Microtubule ,Evolutionary biology ,Molecular evolution ,Genetics ,Animals ,Kinetochores ,Gene ,Phylogeny ,Ecology, Evolution, Behavior and Systematics - Abstract
Centromeres have central functions in chromosome segregation, but centromeric DNA and centromere-binding proteins evolve rapidly in most eukaryotes. The selective pressure(s) underlying the fast evolution of centromere-binding proteins are presently unknown. An attractive possibility is that selfish centromeres promote their preferential inclusion in the oocyte and centromeric proteins evolve to suppress meiotic drive (centromere drive hypothesis). We analysed the selective patterns of mammalian genes that encode kinetochore proteins and microtubule (MT)-destabilizing factors. We show that several of these proteins evolve at the same rate or faster than proteins with a role in centromere specification. Elements of the kinetochore that bind MTs or that bridge the interaction between MTs and the centromere represented the major targets of positive selection. These data are in line with the possibility that the genetic conflict fuelled by meiotic drive extends beyond genes involved in centromere specification. However, we cannot exclude that different selective pressures underlie the rapid evolution of MT-destabilizing factors and kinetochore components. Whatever the nature of such pressures, they must have been constant during the evolution of eutherian mammals, as we found a surprisingly good correlation in dN/dS (ratio of the rate of nonsynonymous and synonymous substitutions) across orders/clades. Finally, when phylogenetic relationships were accounted for, we found little evidence that the evolutionary rates of these genes change with testes size, a proxy for sperm competition. Our data indicate that, in analogy to centromeric proteins, kinetochore components are fast evolving in mammals. This observation may imply that centromere drive plays out at multiple levels or that these proteins adapt to lineage-specific centromeric features.
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- 2021
3. Recent Out-of-Africa Migration of Human Herpes Simplex Viruses
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Chiara Pontremoli, Mario Clerici, Manuela Sironi, Rachele Cagliani, Uberto Pozzoli, and Diego Forni
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0106 biological sciences ,Lineage (genetic) ,Early human migrations ,Herpesvirus 2, Human ,Human Migration ,viruses ,Genome, Viral ,Herpesvirus 1, Human ,Biology ,medicine.disease_cause ,010603 evolutionary biology ,01 natural sciences ,Nucleotide diversity ,03 medical and health sciences ,Phylogenetics ,Genetics ,medicine ,Humans ,Clade ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology ,0303 health sciences ,Herpes Simplex ,Phylogeography ,Herpes simplex virus ,Evolutionary biology ,Africa ,Biological dispersal - Abstract
Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) are ubiquitous human pathogens. Both viruses evolved from simplex viruses infecting African primates and they are thus thought to have left Africa during early human migrations. We analyzed the population structure of HSV-1 and HSV-2 circulating strains. Results indicated that HSV-1 populations have limited geographic structure and the most evident clustering by geography is likely due to recent bottlenecks. For HSV-2, the only level of population structure is accounted for by the so-called “worldwide” and “African” lineages. Analysis of ancestry components and nucleotide diversity, however, did not support the view that the worldwide lineage followed early humans during out-of-Africa dispersal. Although phylogeographic analysis confirmed an African origin for both viruses, molecular dating with a method that corrects for the time-dependent rate phenomenon indicated that HSV-1 and HSV-2 migrated from Africa in relatively recent times. In particular, we estimated that the HSV-2 worldwide lineage left the continent in the 18th century, which corresponds to the height of the transatlantic slave trade, possibly explaining the high prevalence of HSV-2 in the Americas (second highest after Africa). The limited geographic clustering of HSV-1 makes it difficult to date its exit from Africa. The split between the basal clade, containing mostly African sequences, and all other strains was dated at ∼5,000 years ago. Our data do not imply that herpes simplex viruses did not infect early humans but show that the worldwide distribution of circulating strains is the result of relatively recent events.
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- 2020
4. 2020 taxonomic update for phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales
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Amadou A. Sall, Christopher F. Basler, Gary P. Kobinger, Amy J. Lambert, Rodrigo Jardim, John V. da Graça, Yong-Zhen Zhang, Víctor Romanowski, Massimo Turina, John W. McCauley, Lin-Fa Wang, Paul A. Rota, Olga Dolnik, Juan Carlos de la Torre, Gabriele Neumann, Natalie J. Thornburg, Tomohide Natsuaki, Jin Won Song, Kartik Chandran, Carol D. Blair, Michael A. Drebot, Guohui Zhou, Rémi N. Charrel, Heather L. Wells, Ralf G. Dietzgen, Bernadett Pályi, Arnfinn Lodden Økland, Ian Crozier, Gael Kurath, Gilda B. Jonson, Robert R. Martin, Xuejie Yu, Anthony R. Fooks, Renato O. Resende, Ali Mirazimi, Bernadette G. van den Hoogen, Scott Adkins, Colin R. Parrish, Alexander Bukreyev, Anthony Griffiths, Timothy H. Hyndman, Peter Simmonds, Rachel Breyta, Zhìqiáng Wú, Ralf Dürrwald, Jorlan Fernandes, Biao Chen, Udo Hetzel, Alexandro Guterres, Jessica R. Spengler, Michael J. Buchmeier, Rayapati A. Naidu, Janusz T. Paweska, Keizō Tomonaga, Kamil Sarpkaya, Ivan V. Kuzmin, Jens H. Kuhn, Piet Maes, Marco Marklewitz, Masayuki Horie, Arvind Varsani, Shin-Yi Lee Marzano, Ursula J. Buchholz, Jean-Paul Gonzalez, Angelantonio Minafra, Daniela Alioto, Simon J. Anthony, Florian Pfaff, Brian H. Bird, Peter J. Walker, Robert A. Lamb, Noël Tordo, Rainer G. Ulrich, Sergio H. Marshall, Eric M. Leroy, Ayato Takada, Kirsten Spann, Xavier de Lamballerie, John M. Dye, Inmaculada Casas, Manuela Sironi, J. Christopher S. Clegg, Paul Brown, Dennis Rubbenstroth, Yan Liu, Márcio Roberto Teixeira Nunes, Tatjana Avšič-Županc, Martin Verbeek, Andrew J. Easton, Beatriz Navarro, Hideki Ebihara, Benhur Lee, Pierre Formenty, Qi Jin, Hideki Kondō, Eric Bergeron, Sébastien Massart, Daniel R. Perez, S. V. Alkhovsky, Charles H. Calisher, Anna Papa, Xīnglóu Yáng, José A. Navarro, Xifeng Wang, Taiyun Wei, Kim R. Blasdell, Lucie Dufkova, Renata Carvalho de Oliveira, Elba Regina Sampaio de Lemos, Nikos Vasilakis, Pedro Luis Ramos-González, Tong Zhang, Holly R. Hughes, Leonie Forth, Serpil Karadağ, F. Murilo Zerbini, Xueping Zhou, María Laura García, Tomáš Bartonička, Sandra Junglen, Aziz ul Rahman, Petra Straková, Karen E. Keller, William G. Dundon, Jiří Salát, Dexin Li, Jussi Hepojoki, Maria S. Salvato, Hui Wang, Justin Bahl, Bernd Hoffmann, Alberto M. R. Dávila, Jonathan S. Towner, Wénwén Liú, Mifang Liang, Yuri I. Wolf, Gaya K. Amarasinghe, Jianwei Wang, Alex Pauvolid-Corrêa, Anna Maria Vaira, Roy A. Hall, William Marciel de Souza, Thomas Briese, Felicity J. Burt, Valerian V. Dolja, Boris Klempa, Satu Hepojoki, Mengji Cao, Selma Gago-Zachert, Il-Ryong Choi, Rik L. de Swart, Jan Felix Drexler, Gabriel Robles Luna, Igor S. Lukashevich, Maria Minutolo, Amara Jambai, Nihal Buzkan, Steven B. Bradfute, Are Nylund, Ioannis E. Tzanetakis, Xiǎohóng Shí, Stephan Günther, Aura R. Garrison, Takahide Sasaya, Mart Krupovic, Victoria Wahl, Seiji Hongo, Matthew J. Ballinger, María A. Ayllón, Jonas Klingström, David M. Stone, Sead Sabanadzovic, Tracey Goldstein, George Fú Gāo, Aiah Gbakima, Norbert Nowotny, Vicente Pallás, Carina Andrea Reyes, W. Paul Duprex, Roger Hewson, Muhammad Zubair Shabbir, Sophie J. Smither, John V. Williams, Hans Peter Mühlbach, John Chamberlain, Yukio Shirako, Elke Mühlberger, Lies Laenen, Martin Beer, Jiànróng Lǐ, Giovanni P. Martelli, Gustavo Palacios, Sina Bavari, Natalya Yutin, Elena Dal Bó, Michele Digiaro, Jonathan A. Runstadler, John Hammond, Martin Schwemmle, Robert B. Tesh, Dirk Höper, Martin H. Groschup, Francesco Di Serio, Teemu Smura, Sheli R. Radoshitzky, Juliana Freitas-Astúa, Susan Payne, Dennis A. Bente, Anne Balkema-Buschmann, Adolfo García-Sastre, Eugene V. Koonin, Nicholas Di Paola, Bertus K. Rima, Mark D. Stenglein, Mohamed Hassan, Michela Chiumenti, Koray Ergünay, Patrick L. Di Bello, Ron A. M. Fouchier, Anna E. Whitfield, Toufic Elbeaino, Xin Yang, Nicole Mielke-Ehret, Jana Širmarová, Daniel Ruzek, Dàohóng Jiāng, Stanley L. Langevin, Sergey V. Netesov, Zhengli Shi, National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Laboratoire de Ploufragan-Plouzané-Niort [ANSES], Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Virologie des archées - Archaeal Virology, Institut Pasteur [Paris], Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP), Centre collaborateur de l'OMS Arbovirus et Fièvres Hémorragiques virales - Stratégies antivirales (CC-OMS), Institut Pasteur de Guinée, Les Mandinaux, 16450 Le Grand Madieu, This work was supported in part through Laulima Government Solutions, LLC prime contract with the US National Institute of Allergy and Infectious Diseases (NIAID) under Contract No. HHSN272201800013C. J.H.K. performed this work as an employee of Tunnell Government Services (TGS), a subcontractor of Laulima Government Solutions, LLC under Contract No. HHSN272201800013C. This project has been funded in whole or in part with federal funds from the National Cancer Institute (NCI), National Institutes of Health (NIH), under Contract No. 75N91019D00024, Task Order No. 75N91019F00130 to I.C., who was supported by the Clinical Monitoring Research Program Directorate, Frederick National Lab for Cancer Research, sponsored by NCI. This work was also funded in part by Contract No. HSHQDC-15-C-00064 awarded by the US Department of Homeland Security (DHS) Science and Technology Directorate (S&T) for the management and operation of The National Biodefense Analysis and Countermeasures Center (NBACC), a federally funded research and development center operated by the Battelle National Biodefense Institute (V.W.), and NIH contract HHSN272201000040I/HHSN27200004/D04 and grant R24AI120942 (N.V., R.B.T.). S.S. acknowledges partial support from the Special Research Initiative of Mississippi Agricultural and Forestry Experiment Station (MAFES), Mississippi State University, and the National Institute of Food and Agriculture, US Department of Agriculture, Hatch Project 1021494., We thank W. Ian Lipkin and Rafal Tokarz (Columbia University Irving Medical Center, New York, New York, USA) for providing/approving new names for 'blacklegged tick phleboviruses 1 and 3' and Edward Holmes (University of Sydney, Australia) for providing/approving a new name for 'Norway phlebovirus'. Many authors are current members of 2017-2020 International Committee on Taxonomy of Viruses (ICTV) Study Groups: Arenaviridae (Jens H. Kuhn, Michael J. Buchmeier, Rémi N. Charrel, J. Christopher S. Clegg, Juan Carlos de la Torre, Jean-Paul J. Gonzalez, Stephan Günther, Mark D. Stenglein, Jussi Hepojoki, Manuela Sironi, Igor S. Lukashevich, Sheli R. Radoshitzky, Víctor Romanowski, Maria S. Salvato), Artoviridae (Jens H. Kuhn, Ralf G. Dietzgen, Dàohóng Jiāng, Nikos Vasilakis), Aspiviridae (John V. da Graça, Elena Dal Bó, Selma Gago-Zachert, María Laura García, John Hammond, Tomohide Natsuaki, José A. Navarro, Vicente Pallás, Carina A. Reyes, Gabriel Robles Luna, Takahide Sasaya, Ioannis Tzanetakis, Anna Maria Vaira, Martin Verbeek), Bornaviridae (Jens H. Kuhn, Thomas Briese, Ralf Dürrwald, Masayuki Horie, Timothy H. Hyndman, Norbert Nowotny, Susan Payne, Dennis Rubbenstroth, Mark D. Stenglein, Keizō Tomonaga), Bunyavirales (Jens H. Kuhn, Scott Adkins, Juan Carlos de la Torre, Sandra Junglen, Amy J. Lambert, Piet Maes, Marco Marklewitz, Gustavo Palacios, Takahide Sasaya, Yong-Zhen Zhang), Filoviridae (Jens H. Kuhn, Gaya K. Amarasinghe, Christopher Basler, Sina Bavari, Alexander Bukreyev, Kartik Chandran, Ian Crozier, Olga Dolnik, John M. Dye, Pierre B. H. Formenty, Anthony Griffiths, Roger Hewson, Gary Kobinger, Eric M. Leroy, Elke Mühlberger, Sergey V. Netesov, Gustavo Palacios, Bernadett Pályi, Janusz T. Pawęska, Sophie Smither, Ayato Takada, Jonathan S. Towner, Victoria Wahl), Fimoviridae (Michele Digiaro, Toufic Elbeaino, Giovanni P. Martelli, Nicole Mielke-Ehret, Hans-Peter Mühlbach), Hantaviridae (Steven Bradfute, Charles H. Calisher, Boris Klempa, Jonas Klingström, Lies Laenen, Piet Maes, Jin-Won Song, Yong-Zhen Zhang), Jingchuvirales (Nicholas Di Paola), Monjiviricetes (Jens H. Kuhn, Ralf G. Dietzgen, W. Paul Duprex, Dàohóng Jiāng, Piet Maes, Janusz T. Pawęska, Bertus K. Rima, Dennis Rubbenstroth, Peter J. Walker, Yong-Zhen Zhang), Mymonaviridae (María A. Ayllón, Dàohóng Jiāng, Shin-Yi L. Marzano), Nairoviridae (Jens H. Kuhn, Sergey V. Alkhovsky, Tatjana Avšič-Županc, Dennis A. Bente, Éric Bergeron, Felicity Burt, Nicholas Di Paola, Koray Ergünay, Aura R. Garrison, Roger Hewson, Ali Mirazimi, Gustavo Palacios, Anna Papa, Amadou Alpha Sall, Jessica R. Spengler), Negarnaviricota (Jens H. Kuhn, Eugene V. Koonin, Mart Krupovic, Yuri I. Wolf), Nyamiviridae (Jens H. Kuhn, Ralf G. Dietzgen, Dàohóng Jiāng, Nikos Vasilakis), Orthomyxoviridae (Justin Bahl, Inmaculada Casas, Adolfo García-Sastre, Seiji Hongo, Sergio H. Marshall, John W. McCauley, Gabriele Neumann, Colin R. Parrish, Daniel R. Pérez, Jonathan A. Runstadler, Martin Schwemmle), Paramyxoviridae (Anne Balkema-Buschmann, William G. Dundon, W. Paul Duprex, Andrew J. Easton, Ron Fouchier, Gael Kurath, Benhur Lee, Bertus K. Rima, Paul Rota, Lin-Fa Wang, Robobert A. Lamb), Peribunyaviridae (Scott Adkins, Sergey V. Alkhovsky, Martin Beer, Carol D. Blair, Charles H. Calisher, Michael A. Drebot, Holly R. Hughes, Amy J. Lambert, William Marciel de Souza, Marco Marklewitz, Márcio R. T. Nunes, Xiǎohóng Shí), Phasmaviridae (Matthew J. Ballinger, Roy A. Hall, Sandra Junglen, Stanley L. Langevin, Alex Pauvolid-Corrêa), Phenuiviridae (Thomas Briese, Rémi N. Charrel, Xavier De Lamballerie, Hideki Ebihara, George Fú Gāo, Martin H. Groschup, Márcio R. T. Nunes, Gustavo Palacios, Takahide Sasaya, Jin-Won Song), Pneumoviridae (Paul A. Brown, Ursula J. Buchholz, Rik L. de Swart, Jan Felix Drexler, W. Paul Duprex, Andrew J. Easton, Jiànróng Lǐ, Kirsten Spann, Natalie J. Thornburg, Bernadette van den Hoogen, John V. Williams), Rhabdoviridae (Kim R. Blasdell, Rachel Breyta, Ralf G. Dietzgen, Anthony R. Fooks, Juliana Freitas-Astúa, Hideki Kondō, Gael Kurath, Ivan V. Kuzmin, David M. Stone, Robert B. Tesh, Noël Tordo, Nikos Vasilakis, Peter J. Walker, Anna E. Whitfield), Sunviridae (Timothy H. Hyndman, Gael Kurath), Tenuivirus (Il-Ryong Choi, Gilda B. Jonson, Takahide Sasaya, Yukio Shirako, Tàiyún Wèi, Xueping Zhou), and Tospoviridae (Scott Adkins, Amy J. Lambert, Rayapati Naidu, Renato O. Resende, Massimo Turina, Anna E. Whitfield), or are ICTV Executive Committee Members: the 2017–2020 ICTV Chair of the Fungal and Protist Viruses Subcommittee (Peter Simmonds), the 2018–2020 ICTV Proposal Secretary (Peter J. Walker), the 2017–2020 ICTV Chair of the Plant Viruses Subcommittee (F. Murilo Zerbini), the 2017–2020 ICTV Chair of the Animal dsRNA and ssRNA- Viruses Subcommittee (Jens H. Kuhn), and 2017–2020 Elected Members (Sead Sabanadzovic, Arvind Varsani). We would like to thank Anya Crane (NIH/NIAID/DCR/IRF-Frederick) for critically editing the manuscript., NIH - National Institute of Allergy and Infectious Diseases (NIAID) (Estados Unidos), NIH - National Cancer Institute (NCI) (Estados Unidos), United State Department of Homeland Security (Estados Unidos), National Biodefense Analysis and Countermeasures Center (NBACC) (Estados Unidos), Battelle National Biodefense Institute, Mississippi Agricultural and Forestry Experiment Station (MAFES) (Estados Unidos), Mississippi State University (Estados Unidos), United States Department of Agriculture. National Institute of Food and Agriculture, Institut Pasteur [Paris] (IP), Virology, H Kuhn, Jen, Adkins, Scott, Alioto, Daniela, V Alkhovsky, Sergey, K Amarasinghe, Gaya, J Anthony, Simon, Avšič-Županc, Tatjana, A Ayllón, María, Bahl, Justin, Balkema-Buschmann, Anne, J Ballinger, Matthew, Bartonička, Tomáš, Basler, Christopher, Bavari, Sina, Beer, Martin, A Bente, Denni, Bergeron, Éric, H Bird, Brian, Blair, Carol, R Blasdell, Kim, B Bradfute, Steven, Breyta, Rachel, Briese, Thoma, A Brown, Paul, J Buchholz, Ursula, J Buchmeier, Michael, Bukreyev, Alexander, Burt, Felicity, Buzkan, Nihal, H Calisher, Charle, Cao, Mengji, Casas, Inmaculada, Chamberlain, John, Chandran, Kartik, N Charrel, Rémi, Chen, Biao, Chiumenti, Michela, Choi, Il-Ryong, S Clegg, J Christopher, Crozier, Ian, V da Graça, John, Dal Bó, Elena, R Dávila, Alberto M, Carlos de la Torre, Juan, de Lamballerie, Xavier, L de Swart, Rik, L Di Bello, Patrick, Di Paola, Nichola, Di Serio, Francesco, G Dietzgen, Ralf, Digiaro, Michele, V Dolja, Valerian, Dolnik, Olga, A Drebot, Michael, Felix Drexler, Jan, Dürrwald, Ralf, Dufkova, Lucie, G Dundon, William, Paul Duprex, W, M Dye, John, J Easton, Andrew, Ebihara, Hideki, Elbeaino, Toufic, Ergünay, Koray, Fernandes, Jorlan, R Fooks, Anthony, H Formenty, Pierre B, F Forth, Leonie, M Fouchier, Ron A, Freitas-Astúa, Juliana, Gago-Zachert, Selma, Fú Gāo, George, Laura García, María, García-Sastre, Adolfo, R Garrison, Aura, Gbakima, Aiah, Goldstein, Tracey, J Gonzalez, Jean-Paul, Griffiths, Anthony, H Groschup, Martin, Günther, Stephan, Guterres, Alexandro, A Hall, Roy, Hammond, John, Hassan, Mohamed, Hepojoki, Jussi, Hepojoki, Satu, Hetzel, Udo, Hewson, Roger, Hoffmann, Bernd, Hongo, Seiji, Höper, Dirk, Horie, Masayuki, R Hughes, Holly, H Hyndman, Timothy, Jambai, Amara, Jardim, Rodrigo, Jiāng, Dàohóng, Jin, Qi, B Jonson, Gilda, Junglen, Sandra, Karadağ, Serpil, E Keller, Karen, Klempa, Bori, Klingström, Jona, Kobinger, Gary, Kondō, Hideki, V Koonin, Eugene, Krupovic, Mart, Kurath, Gael, V Kuzmin, Ivan, Laenen, Lie, A Lamb, Robert, J Lambert, Amy, L Langevin, Stanley, Lee, Benhur, S Lemos, Elba R, M Leroy, Eric, Li, Dexin, Lǐ, Jiànróng, Liang, Mifang, Liú, Wénwén, Liú, Yàn, S Lukashevich, Igor, Maes, Piet, Marciel de Souza, William, Marklewitz, Marco, H Marshall, Sergio, P Martelli, Giovanni, R Martin, Robert, L Marzano, Shin-Yi, Massart, Sébastien, W McCauley, John, Mielke-Ehret, Nicole, Minafra, Angelantonio, Minutolo, Maria, Mirazimi, Ali, Mühlbach, Hans-Peter, Mühlberger, Elke, Naidu, Rayapati, Natsuaki, Tomohide, Navarro, Beatriz, A Navarro, José, V Netesov, Sergey, Neumann, Gabriele, Nowotny, Norbert, T Nunes, Márcio R, Nylund, Are, L Økland, Arnfinn, C Oliveira, Renata, Palacios, Gustavo, Pallas, Vicente, Pályi, Bernadett, Papa, Anna, R Parrish, Colin, Pauvolid-Corrêa, Alex, T Pawęska, Janusz, Payne, Susan, R Pérez, Daniel, Pfaff, Florian, R Radoshitzky, Sheli, Rahman, Aziz-Ul, L Ramos-González, Pedro, O Resende, Renato, A Reyes, Carina, K Rima, Bertu, Romanowski, Víctor, Robles Luna, Gabriel, Rota, Paul, Rubbenstroth, Denni, A Runstadler, Jonathan, Ruzek, Daniel, Sabanadzovic, Sead, Salát, Jiří, Alpha Sall, Amadou, S Salvato, Maria, Sarpkaya, Kamil, Sasaya, Takahide, Schwemmle, Martin, Z Shabbir, Muhammad, Shí, Xiǎohóng, Shí, Zhènglì, Shirako, Yukio, Simmonds, Peter, Širmarová, Jana, Sironi, Manuela, Smither, Sophie, Smura, Teemu, Song, Jin-Won, M Spann, Kirsten, R Spengler, Jessica, D Stenglein, Mark, M Stone, David, Straková, Petra, Takada, Ayato, B Tesh, Robert, J Thornburg, Natalie, Tomonaga, Keizō, Tordo, Noël, S Towner, Jonathan, Turina, Massimo, Tzanetakis, Ioanni, G Ulrich, Rainer, Maria Vaira, Anna, van den Hoogen, Bernadette, Varsani, Arvind, Vasilakis, Niko, Verbeek, Martin, Wahl, Victoria, J Walker, Peter, Wang, Hui, Wang, Jianwei, Wang, Xifeng, Wang, Lin-Fa, Wèi, Tàiyún, Wells, Heather, E Whitfield, Anna, V Williams, John, I Wolf, Yuri, Wú, Zhìqiáng, Yang, Xin, Yáng, Xīnglóu, Yu, Xuejie, Yutin, Natalya, Murilo Zerbini, F, Zhang, Tong, Zhang, Yong-Zhen, Zhou, Guohui, and Zhou., Xueping
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Species complex ,MESH: Terminology as Topic ,Biología ,VÍRUS DE RNA ,Biology ,Article ,03 medical and health sciences ,Biointeractions and Plant Health ,V?rus / classifica??o ,MESH: Mononegavirales ,Genus ,Virology ,Terminology as Topic ,Life Science ,Bunyavirales ,Ciencias Exactas ,Taxonomy ,030304 developmental biology ,Order Mononegavirales ,0303 health sciences ,030306 microbiology ,Phylum ,General Medicine ,15. Life on land ,Negarnaviricota ,Filogenia ,Taxon ,Evolutionary biology ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Taxonomy (biology) ,Mononegavirales - Abstract
In March 2020, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. At the genus rank, 20 new genera were added, two were deleted, one was moved, and three were renamed. At the species rank, 160 species were added, four were deleted, ten were moved and renamed, and 30 species were renamed. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV., La lista completa de autores que integran el documento puede consultarse en el archivo., Facultad de Ciencias Agrarias y Forestales, Centro de Investigaciones en Fitopatología, Facultad de Ciencias Exactas, Instituto de Biotecnologia y Biologia Molecular
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- 2020
5. An Investigation of the Role of Common and Rare Variants in a Large Italian Multiplex Family of Multiple Sclerosis Patients
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Cristoforo Comi, Filippo Martinelli-Boneschi, Lucia Corrado, Rachele Cagliani, Martina Tosi, Cristina Agliardi, Francesco Favero, Giancarlo Comi, Nadia Barizzone, Melissa Sorosina, Massimo Filippi, Ferdinando Clarelli, Davide Corà, Domenico Caputo, Elisabetta Mascia, Manuela Sironi, Maria Liguori, Chiara Basagni, Vittorio Martinelli, Domizia Vecchio, Miriam Zuccalà, Federica Esposito, Maurizio Leone, Diego Forni, Sandra D'Alfonso, Franca Rosa Guerini, Laura Mendozzi, Barizzone, N., Cagliani, R., Basagni, C., Clarelli, F., Mendozzi, L., Agliardi, C., Forni, D., Tosi, M., Mascia, E., Favero, F., Cora, D., Corrado, L., Sorosina, M., Esposito, F., Zuccala, M., Vecchio, D., Liguori, M., Comi, C., Comi, G., Martinelli, V., Filippi, M., Leone, M., Martinelli-Boneschi, F., Caputo, D., Sironi, M., Guerini, F. R., and D'Alfonso, S.
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Adult ,Male ,DNA Copy Number Variations ,Genetic Linkage ,multiple sclerosis ,multiplex families ,linkage study ,NGS ,rare variants ,Biology ,QH426-470 ,Article ,Multiple sclerosis ,03 medical and health sciences ,0302 clinical medicine ,Missing heritability problem ,Genetic linkage ,Exome Sequencing ,medicine ,Genetics ,Humans ,Multiplex ,Genetic Predisposition to Disease ,Gene ,Exome ,Genetics (clinical) ,Genetic Association Studies ,030304 developmental biology ,Aged ,Linkage study ,Whole genome sequencing ,Aged, 80 and over ,0303 health sciences ,Whole Genome Sequencing ,Genome, Human ,High-Throughput Nucleotide Sequencing ,Rare variants ,Heritability ,Middle Aged ,medicine.disease ,Pedigree ,Italy ,Multiplex families ,Female ,030217 neurology & neurosurgery - Abstract
Known multiple sclerosis (MS) susceptibility variants can only explain half of the disease’s estimated heritability, whereas low-frequency and rare variants may partly account for the missing heritability. Thus, here we sought to determine the occurrence of rare functional variants in a large Italian MS multiplex family with five affected members. For this purpose, we combined linkage analysis and next-generation sequencing (NGS)-based whole exome and whole genome sequencing (WES and WGS, respectively). The genetic burden attributable to known common MS variants was also assessed by weighted genetic risk score (wGRS). We found a significantly higher burden of common variants in the affected family members compared to that observed among sporadic MS patients and healthy controls (HCs). We also identified 34 genes containing at least one low-frequency functional variant shared among all affected family members, showing a significant enrichment in genes involved in specific biological processes—particularly mRNA transport—or neurodegenerative diseases. Altogether, our findings point to a possible pathogenic role of different low-frequency functional MS variants belonging to shared pathways. We propose that these rare variants, together with other known common MS variants, may account for the high number of affected family members within this MS multiplex family.
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- 2021
6. The substitution spectra of coronavirus genomes
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Mario Clerici, Rachele Cagliani, Chiara Pontremoli, Manuela Sironi, and Diego Forni
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APOBEC ,RNA viruses ,transversions ,AcademicSubjects/SCI01060 ,Middle East respiratory syndrome coronavirus ,viruses ,coronavirus ,Context (language use) ,Genome, Viral ,Biology ,medicine.disease_cause ,Evolution, Molecular ,Negative selection ,medicine ,Animals ,Humans ,APOBEC Deaminases ,Molecular Biology ,Pandemics ,Phylogeny ,Coronavirus ,Genetics ,SARS-CoV-2 ,RNA ,COVID-19 ,substitutions ,CpG site ,RNA editing ,Mutation ,Problem Solving Protocol ,transitions ,Information Systems - Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has triggered an unprecedented international effort to sequence complete viral genomes. We leveraged this wealth of information to characterize the substitution spectrum of SARS-CoV-2 and to compare it with those of other human and animal coronaviruses. We show that, once nucleotide composition is taken into account, human and most animal coronaviruses display a mutation spectrum dominated by C to U and G to U substitutions, a feature that is not shared by other positive-sense RNA viruses. However, the proportions of C to U and G to U substitutions tend to decrease as divergence increases, suggesting that, whatever their origin, a proportion of these changes is subsequently eliminated by purifying selection. Analysis of the sequence context of C to U substitutions showed little evidence of apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC)-mediated editing and such contexts were similar for SARS-CoV-2 and Middle East respiratory syndrome coronavirus sampled from different hosts, despite different repertoires of APOBEC3 proteins in distinct species. Conversely, we found evidence that C to U and G to U changes affect CpG dinucleotides at a frequency higher than expected. Whereas this suggests ongoing selective reduction of CpGs, this effect alone cannot account for the substitution spectra. Finally, we show that, during the first months of SARS-CoV-2 pandemic spread, the frequency of both G to U and C to U substitutions increased. Our data suggest that the substitution spectrum of SARS-CoV-2 is determined by an interplay of factors, including intrinsic biases of the replication process, avoidance of CpG dinucleotides and other constraints exerted by the new host.
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- 2021
7. Adaptation of the endemic coronaviruses HCoV-OC43 and HCoV-229E to the human host
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Uberto Pozzoli, Diego Forni, Mario Clerici, Luca De Gioia, Federica Arrigoni, Martino Benvenuti, Rachele Cagliani, Manuela Sironi, Alessandra Mozzi, Forni, D, Cagliani, R, Arrigoni, F, Benvenuti, M, Mozzi, A, Pozzoli, U, Clerici, M, de Gioia, L, and Sironi, M
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viruses ,receptor binding ,Population ,Biology ,Microbiology ,Virus ,Antigenic drift ,endemic coronavirus ,03 medical and health sciences ,Molecular evolution ,positive selection ,Virology ,AcademicSubjects/MED00860 ,Evolutionary dynamics ,education ,molecular dating ,030304 developmental biology ,antigenic drift ,0303 health sciences ,education.field_of_study ,Genetic diversity ,030306 microbiology ,molecular evolution ,Endemic coronaviru ,AcademicSubjects/SCI01130 ,AcademicSubjects/SCI02285 ,virus diseases ,Membrane protein ,Evolutionary biology ,Adaptation ,Research Article - Abstract
Four coronaviruses (HCoV-OC43, HCoV-HKU1, HCoV-NL63, and HCoV-229E) are endemic in human populations. All these viruses are seasonal and generate short-term immunity. Like the highly pathogenic coronaviruses, the endemic coronaviruses have zoonotic origins. Thus, understanding the evolutionary dynamics of these human viruses might provide insight into the future trajectories of SARS-CoV-2 evolution. Because the zoonotic sources of HCoV-OC43 and HCoV-229E are known, we applied a population genetics–phylogenetic approach to investigate which selective events accompanied the divergence of these viruses from the animal ones. Results indicated that positive selection drove the evolution of some accessory proteins, as well as of the membrane proteins. However, the spike proteins of both viruses and the hemagglutinin-esterase (HE) of HCoV-OC43 represented the major selection targets. Specifically, for both viruses, most positively selected sites map to the receptor-binding domains (RBDs) and are polymorphic. Molecular dating for the HCoV-229E spike protein indicated that RBD Classes I, II, III, and IV emerged 3–9 years apart. However, since the appearance of Class V (with much higher binding affinity), around 25 years ago, limited genetic diversity accumulated in the RBD. These different time intervals are not fully consistent with the hypothesis that HCoV-229E spike evolution was driven by antigenic drift. An alternative, not mutually exclusive possibility is that strains with higher affinity for the cellular receptor have out-competed strains with lower affinity. The evolution of the HCoV-OC43 spike protein was also suggested to undergo antigenic drift. However, we also found abundant signals of positive selection in HE. Whereas such signals might result from antigenic drift, as well, previous data showing co-evolution of the spike protein with HE suggest that optimization for human cell infection also drove the evolution of this virus. These data provide insight into the possible trajectories of SARS-CoV-2 evolution, especially in case the virus should become endemic.
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- 2021
8. Alternation between taxonomically divergent hosts is not the major determinant of flavivirus evolution
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Diego Forni, Chiara Pontremoli, Mario Clerici, Manuela Sironi, and Rachele Cagliani
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viruses ,Microbiology ,Genome ,Mosquito-borne flavivirus ,03 medical and health sciences ,Negative selection ,Flaviviridae ,Phylogenetics ,Virology ,biology.animal ,Episodic positive selection ,AcademicSubjects/MED00860 ,Clade ,030304 developmental biology ,0303 health sciences ,Tick-borne flavivirus ,biology ,030306 microbiology ,Dating analysis ,Hosts alternation ,AcademicSubjects/SCI01130 ,AcademicSubjects/SCI02285 ,Vertebrate ,biology.organism_classification ,Flavivirus ,Evolutionary biology ,Flavivirus evolution ,Adaptation ,Research Article - Abstract
Flaviviruses display diverse epidemiological and ecological features. Tick-borne and mosquito-borne flaviviruses (TBFV and MBFV, respectively) are important human pathogens that alternate replication in invertebrate vectors and vertebrate hosts. The Flavivirus genus also includes insect-specific viruses (ISFVs) and viruses with unknown invertebrate hosts. It is generally accepted that viruses that alternate between taxonomically different hosts evolve slowly and that the evolution of MBFVs and TBFVs is dominated by strong constraints, with limited episodes of positive selection. We exploited the availability of flavivirus genomes to test these hypotheses and to compare their rates and patterns of evolution. We estimated the substitution rates of CFAV and CxFV (two ISFVs) and, by taking into account the time-frame of measurement, compared them with those of other flaviviruses. Results indicated that CFAV and CxFV display relatively different substitution rates. However, these data, together with estimates for single-host members of the Flaviviridae family, indicated that MBFVs do not display relatively slower evolution. Conversely, TBFVs displayed some of lowest substitution rates among flaviviruses. Analysis of selective patterns over longer evolutionary time-frames confirmed that MBFVs evolve under strong purifying selection. Interestingly, TBFVs and ISFVs did not show extremely different levels of constraint, although TBFVs alternate among hosts, whereas ISFVs do not. Additional results showed that episodic positive selection drove the evolution of MBFVs, despite their high constraint. Positive selection was also detected on two branches of the TBFVs phylogeny that define the seabird clade. Thus, positive selection was much more common during the evolution of arthropod-borne flaviviruses than previously thought. Overall, our data indicate that flavivirus evolutionary patterns are complex and most likely determined by multiple factors, not limited to the alternation between taxonomically divergent hosts. The frequency of both positive and purifying selection, especially in MBFVs, suggests that a minority of sites in the viral polyprotein experience weak constraint and can evolve to generate new viral phenotypes and possibly promote adaptation to new hosts.
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- 2021
9. Mode and tempo of human hepatitis virus evolution
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Manuela Sironi, Rachele Cagliani, and Diego Forni
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lcsh:Biotechnology ,viruses ,Biophysics ,Human pathogen ,Review Article ,Host switch ,Biology ,TDRP, time-dependent rate phenomenon ,Biochemistry ,Genome ,Zoonosis ,03 medical and health sciences ,0302 clinical medicine ,ORF, open reading frame ,Structural Biology ,lcsh:TP248.13-248.65 ,Genetics ,medicine ,RdRp, RNA-dependent RNA polymerase ,STI, sexually transmitted infection ,NHP, non-human primates ,ComputingMethodologies_COMPUTERGRAPHICS ,030304 developmental biology ,0303 health sciences ,Molecular dating ,medicine.disease ,Computer Science Applications ,Evolutionary biology ,Human hepatitis virus ,030220 oncology & carcinogenesis ,Viral evolution ,TMRCA, time to the most recent common ancestor ,Hepatitis D virus ,Human hepatitis ,Viral hepatitis ,Biotechnology - Abstract
Graphical abstract, Human viral hepatitis, a major cause of morbidity and mortality worldwide, is caused by highly diverse viruses with different genetic, ecological, and pathogenetic features. Technological advances that allow throughput sequencing of viral genomes, as well as the development of computational tools to analyze such genome data, have largely expanded our knowledge on the host range and evolutionary history of human hepatitis viruses. Thus, with the exclusion of hepatitis D virus, close or distant relatives of these human pathogens were identified in a number of domestic and wild mammals. Also, sequences of human viral strains isolated from different geographic locations and over different time-spans have allowed the application of phylogeographic and molecular dating approaches to large viral phylogenies. In this review, we summarize the most recent insights into our understanding of the evolutionary events and ecological contexts that determined the origin and spread of human hepatitis viruses.
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- 2019
10. Genetic Variability of Human Cytomegalovirus Clinical Isolates Correlates With Altered Expression of Natural Killer Cell-Activating Ligands and IFN-γ
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Thomas F. Schulz, Alessandra Coscia, Enrico Bertino, Santo Landolfo, Matteo Biolatti, A. Leone, Rachele Cagliani, Valentina Dell'Oste, Angela Santoni, Marco De Andrea, Cristina Cerboni, Lars Steinbrueck, Ganna Galitska, Manuela Sironi, Simone De Meo, and Diego Forni
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Cytotoxicity, Immunologic ,Male ,0301 basic medicine ,Human cytomegalovirus ,lcsh:Immunologic diseases. Allergy ,Viral pathogenesis ,CD226 ,viruses ,030106 microbiology ,Immunology ,Cytomegalovirus ,Gene Expression ,NK cells ,Biology ,immunomodulation ,GPI-Linked Proteins ,Ligands ,Natural killer cell ,Interferon-gamma ,03 medical and health sciences ,Immune system ,genetic variability ,medicine ,Humans ,Immunology and Allergy ,Genetic variability ,innate immunity ,Cells, Cultured ,Original Research ,Immune Evasion ,next generation sequencing ,Innate immune system ,Reverse Transcriptase Polymerase Chain Reaction ,Genetic Variation ,High-Throughput Nucleotide Sequencing ,medicine.disease ,NKG2D ,congenital infection ,Killer Cells, Natural ,030104 developmental biology ,medicine.anatomical_structure ,NK Cell Lectin-Like Receptor Subfamily K ,Cytomegalovirus Infections ,Intercellular Signaling Peptides and Proteins ,human cytomegalovirus (HCMV) ,lcsh:RC581-607 ,multiple-strain infection - Abstract
Human cytomegalovirus (HCMV) infection often leads to systemic disease in immunodeficient patients and congenitally infected children. Despite its clinical significance, the exact mechanisms contributing to HCMV pathogenesis and clinical outcomes have yet to be determined. One of such mechanisms involves HCMV-mediated NK cell immune response, which favors viral immune evasion by hindering NK cell-mediated cytolysis. This process appears to be dependent on the extent of HCMV genetic variation as high levels of variability in viral genes involved in immune escape have an impact on viral pathogenesis. However, the link between viral genome variations and their functional effects has so far remained elusive. Thus, here we sought to determine whether inter-host genetic variability of HCMV influences its ability to modulate NK cell responses to infection. For this purpose, five HCMV clinical isolates from a previously characterized cohort of pediatric patients with confirmed HCMV congenital infection were evaluated by next-generation sequencing (NGS) for genetic polymorphisms, phylogenetic relationships, and multiple-strain infection. We report variable levels of genetic characteristics among the selected clinical strains, with moderate variations in genome regions associated with modulation of NK cell functions. Remarkably, we show that different HCMV clinical strains differentially modulate the expression of several ligands for the NK cell-activating receptors NKG2D, DNAM-1/CD226, and NKp30. Specifically, the DNAM-1/CD226 ligand PVR/CD155 appears to be predominantly upregulated by fast-replicating (“aggressive”) HCMV isolates. On the other hand, the NGK2D ligands ULBP2/5/6 are downregulated regardless of the strain used, while other NK cell ligands (i.e., MICA, MICB, ULBP3, Nectin-2/CD112, and B7-H6) are not significantly modulated. Furthermore, we show that IFN-γ; production by NK cells co-cultured with HCMV-infected fibroblasts is directly proportional to the aggressiveness of the HCMV clinical isolates employed. Interestingly, loss of NK cell-modulating genes directed against NK cell ligands appears to be a common feature among the “aggressive” HCMV strains, which also share several gene variants across their genomes. Overall, even though further studies based on a higher number of patients would offer a more definitive scenario, our findings provide novel mechanistic insights into the impact of HCMV genetic variability on NK cell-mediated immune responses.
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- 2021
11. Correction to: 2021 Taxonomic update of phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales
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Martin Schwemmle, S. V. Alkhovsky, Mark D. Stenglein, Jinguo Zhang, Shaohua Wen, Víctor Romanowski, Massimo Turina, Peter J. Walker, Baldwyn Torto, Paul A. Rota, Xavier de Lamballerie, Stuart G. Siddell, Noël Tordo, John M. Dye, Inmaculada Casas, Andrew J. Easton, Yasuhiro Tomitaka, Eugene V. Koonin, J. Christopher S. Clegg, Judith K. Brown, Kartik Chandran, Carol D. Blair, Shinya Tsuda, Tony L. Goldberg, Andrew J. Bennett, Ralf G. Dietzgen, Koray Ergünay, Aura R. Garrison, Jiang Hong, Kim R. Blasdell, Matthew J. Ballinger, Zuokun Yang, Manuela Sironi, Florian Hüttner, Timothy H. Hyndman, D. A. Patterson, Roy A. Hall, Eric M. Leroy, Liying Qi, Risto Jalkanen, Gary P. Kobinger, Yanxiang Wang, Michael A. Drebot, Emiliano Di Cicco, Martin H. Groschup, Amy K. Teffer, Thomas S. Postler, Sophie J. Smither, Ni Hong, Sina Bavari, Jamie Bojko, Amy Tabata, Michael J. Buchmeier, Sébastien Massart, Daniel R. Perez, Hironobu Yanagisawa, Janice Uchida, Xiǎohóng Shí, Marina Ciuffo, Jean-Paul Gonzalez, Brian H. Bird, Alejandro Olmedo-Velarde, Justin Bahl, Tao Hu, J. Felix Drexler, Gaya K. Amarasinghe, Jens H. Kuhn, Shaorong Li, Taiyun Wei, Sandra Junglen, José A. Navarro, Sofia Paraskevopoulou, Hans Peter Mühlbach, Nicholas Di Paola, Toufic Elbeaino, Guoping Wang, Song Zhang, Tong Han, Yukio Shirako, Pierre Formenty, Anthony R. Fooks, Lifeng Zhai, Benhur Lee, María Laura García, Dag-Ragnar Blystad, Bertus K. Rima, William G. Dundon, Hideki Ebihara, Jiangxiang Wu, John S. Hu, Gabriel Robles Luna, Jana Fránová, Maria S. Salvato, Norbert Nowotny, Carina Andrea Reyes, Kristina M. Miller, Eric Bergeron, Renato O. Resende, Holly R. Hughes, Victoria Wahl, Changchun Tu, Anna Papa, Roger Hewson, Anna Maria Vaira, Nicolás Bejerman, Alex Pauvolid-Corrêa, Seiji Hongo, Igor S. Lukashevich, Michael Kawate, Bernard R. Agwanda, Sead Sabanadzovic, Gideon J. Mordecai, Piet Maes, Steven B. Bradfute, Stephan Günther, Michele Digiaro, Tomio Usugi, Zhe Zhang, Adam C. Park, Guy Smagghe, Shin-Yi Lee Marzano, Kenji Kubota, Ioannis E. Tzanetakis, Christopher F. Basler, Rik L. de Swart, Yong-Zhen Zhang, Felicity J. Burt, Curtis A. Suttle, Mart Krupovic, Jussi Hepojoki, John W. McCauley, Jonathan S. Towner, Charles H. Calisher, Lei Xu, George Fú Gāo, Jonathan A. Runstadler, David M. Stone, Karia H. Kaukinen, Rachel Breyta, Masayuki Horie, Gael Kurath, Carmen Büttner, Lin-Fa Wang, Jessica R. Spengler, Olga Dolnik, Yuya Chiaki, Nicole Mielke-Ehret, Robert B. Tesh, Gustavo Palacios, Marco Chiapello, Tatjana Avšič-Županc, Martin Verbeek, Qi Cheng, Scott Adkins, Elena Dal Bó, Fujio Kadono, Selma Gago-Zachert, Sergio H. Marshall, Marta Vallino, Gilda B. Jonson, Jingjing Fu, Rosemary Sang, Takahide Sasaya, Amy J. Lambert, Paul Brown, Dennis Rubbenstroth, Dennis A. Bente, Colin R. Parrish, Jin Won Song, María A. Ayllón, Shigeharu Takeuchi, Arvind Varsani, Dàohóng Jiāng, Natalie J. Thornburg, Michael J. Melzer, Stanley L. Langevin, Igor Koloniuk, Mang Shi, John Hammond, Vicente Pallás, Thomas Briese, Amadou A. Sall, Jari Sugano, Sergey V. Netesov, Zhengli Shi, M. Ilyas, Yoshifumi Shimomoto, Wayne B. Borth, Anna E. Whitfield, Ayato Takada, Kirsten Spann, W. Paul Duprex, Marco Forgia, Jiro Wada, Susanne von Bargen, Rim Al Kubrusli, Tobi J. Ming, Gabriele Neumann, Rémi N. Charrel, Caixia Yang, Rayapati A. Naidu, Ralf Dürrwald, David P. Tchouassi, Ursula J. Buchholz, Carlotta Peracchio, Tomohide Natsuaki, Anthony Griffiths, Sheli R. Radoshitzky, Márcio Roberto Teixeira Nunes, Juliana Freitas-Astúa, Janusz T. Paweska, Humberto Debat, Francesco Di Serio, Stephanie Fürl, Susan Payne, Hugh W. Ferguson, Juan Carlos de la Torre, Keizō Tomonaga, Muhammad Waqas, Longhui Li, Elke Mühlberger, Bernadett Pályi, Lies Laenen, Ian Crozier, Yuri I. Wolf, Bernadette G. van den Hoogen, Martin Beer, Jiànróng Lǐ, Thomas Gaskin, Mengji Cao, Ali Mirazimi, F. Murilo Zerbini, Peter Simmonds, Anne Balkema-Buschmann, Adolfo García-Sastre, Hideki Kondō, William Marciel de Souza, Huazhen Liu, John V. Williams, Marco Marklewitz, Alexander Bukreyev, Luisa Rubino, Angela D. Schulze, Nolwenn M. Dheilly, Xueping Zhou, Nikos Vasilakis, Elliot J. Lefkowitz, Boris Klempa, Il-Ryong Choi, Yaqin Wang, and Jonas Klingström
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Biointeractions and Plant Health ,biology ,Phylum ,Virology ,Life Science ,Bunyavirales ,General Medicine ,Mononegavirales ,biology.organism_classification ,Virology & Molecular Biology ,Virologie & Moleculaire Biologie - Abstract
Unfortunately, the inclusion of original names (in non-Latin script) of the following authors caused problems with author name indexing in PubMed. Therefore, these original names were removed from XML data to correct the PubMed record. Mengji Cao, Yuya Chiaki, Hideki Ebihara, Jingjing Fu, George Fú Gāo, Tong Han, Jiang Hong, Ni Hong, Seiji Hongo, Masayuki Horie, Dàohóng Jiāng, Fujio Kadono, Hideki Kondō, Kenji Kubota, Shaorong Li, Longhui Li, Jiànróng Lǐ, Huazhen Liu, Tomohide Natsuaki, Sergey V. Netesov, Anna Papa, Sofia Paraskevopoulou, Liying Qi, Takahide Sasaya, Mang Shi, Xiǎohóng Shí, Zhènglì Shí, Yoshifumi Shimomoto, Jin‑Won Song, Ayato Takada, Shigeharu Takeuchi, Yasuhiro Tomitaka, Keizō Tomonaga, Shinya Tsuda, Changchun Tu, Tomio Usugi, Nikos Vasilakis, Jiro Wada, Lin‑Fa Wang, Guoping Wang, Yanxiang Wang, Yaqin Wang, Tàiyún Wèi, Shaohua Wen, Jiangxiang Wu, Lei Xu, Hironobu Yanagisawa, Caixia Yang, Zuokun Yang, Lifeng Zhai, Yong‑Zhen Zhang, Song Zhang, Jinguo Zhang, Zhe Zhang, Xueping Zhou. In addition, the publication call-out in the supplementary material was updated from issue 11 to issue 12. The original article has been corrected.
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- 2021
12. Recombination and Positive Selection Differentially Shaped the Diversity of Betacoronavirus Subgenera
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Diego Forni, Rachele Cagliani, and Manuela Sironi
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0301 basic medicine ,Genome evolution ,030106 microbiology ,coronavirus ,lcsh:QR1-502 ,Biology ,genome evolution ,medicine.disease_cause ,lcsh:Microbiology ,03 medical and health sciences ,Genus ,positive selection ,Virology ,medicine ,Coronavirus ,virus evolution ,Host (biology) ,biology.organism_classification ,recombination ,betacoronavirus ,030104 developmental biology ,Infectious Diseases ,Evolutionary biology ,Viral evolution ,Subgenus ,Betacoronavirus ,Recombination - Abstract
The Betacoronavirus genus of mammal-infecting viruses includes three subgenera (Sarbecovirus, Embecovirus, and Merbecovirus), in which most known human coronaviruses, including SARS-CoV-2, cluster. Coronaviruses are prone to host shifts, with recombination and positive selection possibly contributing to their high zoonotic potential. We analyzed the role of these two forces in the evolution of viruses belonging to the Betacoronavirus genus. The results showed that recombination has been pervasive during sarbecovirus evolution, and it is more widespread in this subgenus compared to the other two. In both sarbecoviruses and merbecoviruses, recombination hotspots are clearly observed. Conversely, positive selection was a less prominent force in sarbecoviruses compared to embecoviruses and merbecoviruses and targeted distinct genomic regions in the three subgenera, with S being the major target in sarbecoviruses alone. Overall, the results herein indicate that Betacoronavirus subgenera evolved along different trajectories, which might recapitulate their host preferences or reflect the origins of the presently available coronavirus sequences.
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- 2020
13. Coding potential and sequence conservation of SARS-CoV-2 and related animal viruses
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Rachele Cagliani, Manuela Sironi, Diego Forni, and Mario Clerici
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0301 basic medicine ,Coding potential ,Coronaviruses ,viruses ,dN, nonsynonymous substitution rate ,Genome ,Homology (biology) ,ORFS ,skin and connective tissue diseases ,Phylogeny ,Genetics ,GTR, General Time Reversible ,Recombination, Genetic ,dS, synonymous substitution rate ,biology ,virus diseases ,Infectious Diseases ,SLAC, single-likelihood ancestor counting ,RNA, Viral ,Coronavirus Infections ,PAML, Phylogenetic Analysis by Maximum Likelihood ,Gene Expression Regulation, Viral ,Microbiology (medical) ,030106 microbiology ,Functional RNA elements ,Pneumonia, Viral ,Sequence alignment ,Genome, Viral ,Microbiology ,Ribosomal frameshift ,Article ,03 medical and health sciences ,Betacoronavirus ,ORF, open reading frame ,Phylogenetics ,Animals ,Humans ,Gene ,Pandemics ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,SARS-CoV-2 ,fungi ,1 PRF, programmed -1 ribosomal frameshifting ,COVID-19 ,biology.organism_classification ,body regions ,030104 developmental biology ,Sequence Alignment - Abstract
In December 2019, a novel human-infecting coronavirus (SARS-CoV-2) was recognized in China. In a few months, SARS-CoV-2 has caused thousands of disease cases and deaths in several countries. Phylogenetic analyses indicated that SARS-CoV-2 clusters with SARS-CoV in the Sarbecovirus subgenus and viruses related to SARS-CoV-2 were identified from bats and pangolins. Coronaviruses have long and complex genomes with high plasticity in terms of gene content. To date, the coding potential of SARS-CoV-2 remains partially unknown. We thus used available sequences of bat and pangolin viruses to determine the selective events that shaped the genome structure of SARS-CoV-2 and to assess its coding potential. By searching for signals of significantly reduced variability at synonymous sites (dS), we identified six genomic regions, one of these corresponding to the programmed −1 ribosomal frameshift. The most prominent signal of dS reduction was observed within the E gene. A genome-wide analysis of conserved RNA structures indicated that this region harbors a putative functional RNA element that is shared with the SARS-CoV lineage. Additional signals of reduced dS indicated the presence of internal ORFs. Whereas the presence ORF9a (internal to N) was previously proposed by homology with a well characterized protein of SARS-CoV, ORF3h (for hypothetical, within ORF3a) was not previously described. The predicted product of ORF3h has 90% identity with the corresponding predicted product of SARS-CoV and displays features suggestive of a viroporin. Finally, analysis of the putative ORF10 revealed high dN/dS (3.82) in SARS-CoV-2 and related coronaviruses. In the SARS-CoV lineage, the ORF is predicted to encode a truncated protein and is neutrally evolving. These data suggest that ORF10 encodes a functional protein in SARS-CoV-2 and that positive selection is driving its evolution. Experimental analyses will be necessary to validate and characterize the coding and non-coding functional elements we identified., Highlights • We analyzed the coding region of SARS-CoV-2 and related bat/pangolin viruses. • We identified six regions of significantly low variability at sysnonymous sites. • One of these corresponds to a conserved RNA structure shared with the SARS-CoV lineage. • The dS reduction within ORF3a corresponds to a potential ORF encoding a viroporin. • In SARS-CoV-2 and related viruses, the putative 3′ terminal ORF10 has high dN/dS.
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- 2020
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14. Simplexviruses successfully adapt to their host by fine-tuning immune responses
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Uberto Pozzoli, Mario Clerici, Rachele Cagliani, Chiara Pontremoli, Marina Saresella, Alessandra Mozzi, Manuela Sironi, Mara Biasin, Diego Forni, and Irma Saulle
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chemistry.chemical_classification ,Genetics ,Simplexvirus ,food.ingredient ,Mutant ,Human leukocyte antigen ,Biology ,Virus ,Amino acid ,Immune system ,food ,chemistry ,Antigen ,Glycoprotein - Abstract
Primate herpes simplex viruses are relatively harmless to their natural hosts, whereas cross-species transmission can result in severe disease. We performed a genome-wide scan for signals of adaptation of simplexviruses to hominins. We found evidence of positive selection in three glycoproteins, with selected sites located in antigenic determinants. Positively selected non-core proteins were involved in different immune-escape mechanisms. By expressing mutants of one of these proteins (ICP47), we show that the amino acid status at the positively selected sites is sufficient to induce HLA-G. HSV-1/HSV-2 ICP47 induced HLA-G when mutated to recapitulate residues in B virus, whereas the mutated version of B virus ICP47 failed to determine HLA-G expression. Thus, the evolution of ICP47 in HSV-1/HSV-2 determined the loss of an immunosuppressive effect, suggesting that simplexviruses tune immune responses to promote successful co-existence with their hosts. These results also help explain the high pathogenicity of B virus in humans.
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- 2020
15. Antigenic variation of SARS-CoV-2 in response to immune pressure
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Uberto Pozzoli, Chiara Pontremoli, Rachele Cagliani, Manuela Sironi, Diego Forni, Mario Clerici, and Alessandra Mozzi
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0106 biological sciences ,0301 basic medicine ,T cell ,viruses ,Population ,Biology ,010603 evolutionary biology ,01 natural sciences ,Genome ,SARS‐CoV‐2 ,Virus ,Epitope ,03 medical and health sciences ,Immune system ,COVID‐19 ,medicine ,Genetics ,Antigenic variation ,education ,human coronavirus ,Ecology, Evolution, Behavior and Systematics ,chemistry.chemical_classification ,education.field_of_study ,Original Articles ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,B cell epitope ,Original Article ,sarbecovirus ,Glycoprotein ,T cell epitope ,CD8 - Abstract
Analysis of the bat viruses most closely related to SARS‐CoV‐2 indicated that the virus probably required limited adaptation to spread in humans. Nonetheless, since its introduction in human populations, SARS‐CoV‐2 must have been subject to the selective pressure imposed by the human immune system. We exploited the availability of a large number of high‐quality SARS‐CoV‐2 genomes, as well as of validated epitope predictions, to show that B cell epitopes in the spike glycoprotein (S) and in the nucleocapsid protein (N) have higher diversity than nonepitope positions. Similar results were obtained for other human coronaviruses and for sarbecoviruses sampled in bats. Conversely, in the SARS‐CoV‐2 population, epitopes for CD4+ and CD8+ T cells were not more variable than nonepitope positions. A significant reduction in epitope variability was instead observed for some of the most immunogenic proteins (S, N, ORF8 and ORF3a). Analysis over longer evolutionary time frames indicated that this effect is not due to differential constraints. These data indicate that SARS‐CoV‐2 evolves to elude the host humoral immune response, whereas recognition by T cells is not actively avoided by the virus. However, we also found a trend of lower diversity of T cell epitopes for common cold coronaviruses, indicating that epitope conservation per se is not directly linked to disease severity. We suggest that conservation serves to maintain epitopes that elicit tolerizing T cell responses or induce T cells with regulatory activity.
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- 2020
16. Computational Inference of Selection Underlying the Evolution of the Novel Coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2
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Manuela Sironi, Rachele Cagliani, Mario Clerici, and Diego Forni
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Models, Molecular ,viruses ,Pneumonia, Viral ,Immunology ,Population ,Genome, Viral ,Biology ,spike protein ,medicine.disease_cause ,Microbiology ,N protein ,Evolution, Molecular ,viral evolution ,Betacoronavirus ,Open Reading Frames ,Viral Proteins ,Negative selection ,positive selection ,Molecular evolution ,Chiroptera ,Virology ,medicine ,Nsp1 ,Animals ,Humans ,Amino Acid Sequence ,Selection, Genetic ,ORFS ,education ,Pandemics ,Phylogeny ,Coronavirus ,education.field_of_study ,Natural selection ,SARS-CoV-2 ,COVID-19 ,ORF8 ,biology.organism_classification ,Genetic Diversity and Evolution ,Evolutionary biology ,Insect Science ,Viral evolution ,Coronavirus Infections - Abstract
Coronaviruses are dangerous zoonotic pathogens; in the last 2 decades, three coronaviruses have crossed the species barrier and caused human epidemics. One of these is the recently emerged SARS-CoV-2. We investigated how, since its divergence from a closely related bat virus, natural selection shaped the genome of SARS-CoV-2. We found that distinct coding regions in the SARS-CoV-2 genome evolved under conditions of different degrees of constraint and are consequently more or less prone to tolerate amino acid substitutions. In practical terms, the level of constraint provides indications about which proteins/protein regions are better suited as possible targets for the development of antivirals or vaccines. We also detected limited signals of positive selection in three viral ORFs. However, we warn that, in the absence of knowledge about the chain of events that determined the human spillover, these signals should not be necessarily interpreted as evidence of an adaptation to our species., The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that recently emerged in China is thought to have a bat origin, as its closest known relative (BatCoV RaTG13) was described previously in horseshoe bats. We analyzed the selective events that accompanied the divergence of SARS-CoV-2 from BatCoV RaTG13. To this end, we applied a population genetics-phylogenetics approach, which leverages within-population variation and divergence from an outgroup. Results indicated that most sites in the viral open reading frames (ORFs) evolved under conditions of strong to moderate purifying selection. The most highly constrained sequences corresponded to some nonstructural proteins (nsps) and to the M protein. Conversely, nsp1 and accessory ORFs, particularly ORF8, had a nonnegligible proportion of codons evolving under conditions of very weak purifying selection or close to selective neutrality. Overall, limited evidence of positive selection was detected. The 6 bona fide positively selected sites were located in the N protein, in ORF8, and in nsp1. A signal of positive selection was also detected in the receptor-binding motif (RBM) of the spike protein but most likely resulted from a recombination event that involved the BatCoV RaTG13 sequence. In line with previous data, we suggest that the common ancestor of SARS-CoV-2 and BatCoV RaTG13 encoded/encodes an RBM similar to that observed in SARS-CoV-2 itself and in some pangolin viruses. It is presently unknown whether the common ancestor still exists and, if so, which animals it infects. Our data, however, indicate that divergence of SARS-CoV-2 from BatCoV RaTG13 was accompanied by limited episodes of positive selection, suggesting that the common ancestor of the two viruses was poised for human infection. IMPORTANCE Coronaviruses are dangerous zoonotic pathogens; in the last 2 decades, three coronaviruses have crossed the species barrier and caused human epidemics. One of these is the recently emerged SARS-CoV-2. We investigated how, since its divergence from a closely related bat virus, natural selection shaped the genome of SARS-CoV-2. We found that distinct coding regions in the SARS-CoV-2 genome evolved under conditions of different degrees of constraint and are consequently more or less prone to tolerate amino acid substitutions. In practical terms, the level of constraint provides indications about which proteins/protein regions are better suited as possible targets for the development of antivirals or vaccines. We also detected limited signals of positive selection in three viral ORFs. However, we warn that, in the absence of knowledge about the chain of events that determined the human spillover, these signals should not be necessarily interpreted as evidence of an adaptation to our species.
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- 2020
17. Population structure of Lassa Mammarenavirus in West Africa
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Diego Forni and Manuela Sironi
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0301 basic medicine ,viruses ,030231 tropical medicine ,Population ,Population structure ,lcsh:QR1-502 ,Lassa mammarenavirus ,Genome, Viral ,Biology ,Disease cluster ,Article ,lcsh:Microbiology ,West africa ,03 medical and health sciences ,0302 clinical medicine ,Lassa Fever ,Virology ,parasitic diseases ,geographic distribution ,medicine ,Humans ,Lassa fever ,education ,Lassa virus ,Phylogeny ,education.field_of_study ,Genetic diversity ,disease outcome ,Strain (biology) ,population structure ,Biodiversity ,medicine.disease ,Africa, Western ,Phylogeography ,030104 developmental biology ,Infectious Diseases ,Genetics, Population ,Evolutionary biology ,ancestry component ,Mammarenavirus - Abstract
Lassa mammarenavirus (LASV) is the etiologic agent of Lassa fever. In endemic regions in West Africa, LASV genetic diversity tends to cluster by geographic area. Seven LASV lineages are recognized, but the role of viral genetic determinants on disease presentation in humans is uncertain. We investigated the geographic structure and distribution of LASV in West Africa. We found strong spatial clustering of LASV populations, with two major east&ndash, west and north&ndash, south diversity gradients. Analysis of ancestry components indicated that known LASV lineages diverged from an ancestral population that most likely circulated in Nigeria, although alternative locations, such as Togo, cannot be excluded. Extant sequences carrying the largest contribution of this ancestral population include the prototype Pinneo strain, the Togo isolates, and a few viruses isolated in Nigeria. The LASV populations that experienced the strongest drift circulate in Mali and the Ivory Coast. By focusing on sequences form a single LASV sublineage (IIg), we identified an ancestry component possibly associated with protection from a fatal disease outcome. Although the same ancestry component tends to associate with lower viral loads in plasma, the small sample size requires that these results are treated with extreme caution.
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- 2020
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18. Evolutionary analysis of exogenous and integrated HHV-6A/HHV-6B populations
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Uberto Pozzoli, Manuela Sironi, Diego Forni, Mario Clerici, and Rachele Cagliani
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viruses ,Population ,Population structure ,Microbiology ,Genome ,Nucleotide diversity ,HHV-6 ,viral evolution ,03 medical and health sciences ,Virology ,education ,030304 developmental biology ,0303 health sciences ,education.field_of_study ,biology ,030306 microbiology ,virus diseases ,population structure ,biology.organism_classification ,Evolutionary biology ,Viral genomes ,Human betaherpesvirus ,Viral evolution ,Geographic origin ,Roseolovirus ,Research Article - Abstract
Human betaherpesviruses 6A and 6B (HHV-6A and HHV-6B) are highly prevalent in human populations. The genomes of these viruses can be stably integrated at the telomeres of human chromosomes and be vertically transmitted (inherited chromosomally integrated HHV-6A/HHV-6B, iciHHV-6A/iciHHV-6B). We reconstructed the population structures of HHV-6A and HHV-6B, showing that HHV-6A diverged less than HHV-6B genomes from the projected common ancestral population. Thus, HHV-6B genomes experienced stronger drift, as also supported by calculation of nucleotide diversity and Tajima’s D. Analysis of ancestry proportions indicated that HHV-6A exogenous viruses and iciHHV-6A derived most of their genomes from distinct ancestral sources. Conversely, ancestry proportions were similar in exogenous HHV-6B viruses and iciHHV-6B. In line with previous indications, this suggests the distinct exogenous viral populations that originated iciHHV-6B in subjects with European and Asian ancestry are still causing infections in the corresponding geographic areas. Notably, for both iciHHV-6A and iciHHV-6B, we found that European and American sequences tend to have high proportions of ancestry from viral populations that experienced considerable drift, suggesting that they underwent one or more bottlenecks followed by population expansion. Finally, analysis of HHV-6B exogenous viruses sampled in Japan indicated that proportions of ancestry components of most of these viruses are different from the majority of those sampled in the USA. More generally, we show that, in both viral species, both integrated and exogenous viral genomes have different ancestry components, partially depending on geographic location. It would be extremely important to determine whether such differences account for the diversity of HHV-6A/HHV-6B-associated clinical symptoms and epidemiology. Also, the sequencing of additional exogenous and integrated viral genomes will be instrumental to confirm and expand our conclusions, which are based on a relatively small number of genomes, sequenced with variable quality, and with unequal sampling in terms of geographic origin.
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- 2020
19. Intrinsically disordered regions are abundant in simplexvirus proteomes and display signatures of positive selection
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Uberto Pozzoli, Diego Forni, Rachele Cagliani, Mario Clerici, Manuela Sironi, and Alessandra Mozzi
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Genetics ,0303 health sciences ,Simplexvirus ,food.ingredient ,Host (biology) ,viruses ,Positive selection ,030302 biochemistry & molecular biology ,Protein domain ,Biology ,HSV-2 ,Microbiology ,C content ,Genome ,virus–host interactors ,03 medical and health sciences ,food ,positive selection ,Virology ,Proteome ,simplexviruses ,Adaptation ,intrinsically disordered regions (IDRs) ,Research Article ,030304 developmental biology - Abstract
Whereas the majority of herpesviruses co-speciated with their mammalian hosts, human herpes simplex virus 2 (HSV-2, genus Simplexvirus) most likely originated from the cross-species transmission of chimpanzee herpesvirus 1 to an ancestor of modern humans. We exploited the peculiar evolutionary history of HSV-2 to investigate the selective events that drove herpesvirus adaptation to a new host. We show that HSV-2 intrinsically disordered regions (IDRs)—that is, protein domains that do not adopt compact three-dimensional structures—are strongly enriched in positive selection signals. Analysis of viral proteomes indicated that a significantly higher portion of simplexvirus proteins is disordered compared with the proteins of other human herpesviruses. IDR abundance in simplexvirus proteomes was not a consequence of the base composition of their genomes (high G + C content). Conversely, protein function determines the IDR fraction, which is significantly higher in viral proteins that interact with human factors. We also found that the average extent of disorder in herpesvirus proteins tends to parallel that of their human interactors. These data suggest that viruses that interact with fast-evolving, disordered human proteins, in turn, evolve disordered viral interactors poised for innovation. We propose that the high IDR fraction present in simplexvirus proteomes contributes to their wider host range compared with other herpesviruses.
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- 2020
20. Retraction to: A complex evolutionary relationship between HHV-6A and HHV-6B
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Uberto Pozzoli, Mario Clerici, Manuela Sironi, Diego Forni, and Rachele Cagliani
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0303 health sciences ,education.field_of_study ,Genetic diversity ,030306 microbiology ,viruses ,Population size ,Population ,virus diseases ,biochemical phenomena, metabolism, and nutrition ,Biology ,Disease cluster ,Microbiology ,Genome ,Nucleotide diversity ,Telomere ,03 medical and health sciences ,Evolutionary biology ,Virology ,education ,Recombination ,030304 developmental biology - Abstract
Human betaherpesviruses 6A and 6B (HHV-6A and HHV-6B) are highly prevalent in human populations. The genomes of these viruses can be stably integrated at the telomeres of human chromosomes and be vertically transmitted (inherited chromosomally integrated HHV-6, iciHHV6). We reconstructed the population structure of HHV-6 and we show that HHV-6A genomes diverged less than HHV-6B genomes from the ancestral common HHV-6A/B population. Analysis of ancestry proportions indicated that HHV-6A exogenous viruses and iciHHV-6A derived most of their genomes from distinct ancestral sources. Conversely, exogenous viral and iciHHV-6B populations were similar in terms of ancestry components, with no evident geographic structuring. Most HHV-6B genomes sampled to date derive from viral populations that experienced considerable drift. However, a population of HHV-6 exogenous viruses, currently classified as HHV-6B and sampled in New York state, formed a separate cluster (NY cluster) and harbored a considerable portion of HHV-6A-like ancestry. Recombination detection methods identified these viruses as interspecies recombinants, but phylogenetic reconstruction indicated that the recombination signals are due to shared ancestry. In analogy to iciHHV-6A, NY cluster viruses have high nucleotide diversity and constant population size. We propose that HHV-6A sequences and the NY cluster population diverged from an ancestral HHV-6A-like population. A relatively recent bottleneck of the NY (or a related) population with subsequent expansion originated most HHV-6B genomes currently sampled. Our findings indicate that the distinction between HHV-6A and -6B is not as clear-cut as previously thought. More generally, epidemiological and clinical surveys would benefit from taking HHV-6 genetic diversity into account.
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- 2019
21. Genetic susceptibility to infectious diseases: Current status and future perspectives from genome-wide approaches
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Chiara Pontremoli, Manuela Sironi, and Alessandra Mozzi
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0301 basic medicine ,T2D, Type 2 diabetes ,TB, tuberculosis ,Genome-wide association study ,Adaptive Immunity ,Bioinformatics ,Genome ,eQTL, expression quantitative trait locus ,lncRNA, long non-coding RNA ,CJD, Creutzfeldt-Jacob disease ,0302 clinical medicine ,PCA, principal components analysis ,GWAS ,KIR, Killer-cell immunoglobulin-like receptor ,Infectious disease ,SNP, single nucleotide polymorphism ,Biological Evolution ,3. Good health ,Infectious Diseases ,IAV, Influenza A virus ,WNV, West Nile virus ,Phenotype ,HCV, hepatitis C virus ,HPV, Human Papillomavirus ,Host-Pathogen Interactions ,EBOV, Ebola virus ,GWAS, Genome-wide association study ,Microbiology (medical) ,LD, linkage disequilibrium ,Quantitative Trait Loci ,CNV, copy number variant ,Computational biology ,Human leukocyte antigen ,Biology ,Microbiology ,Communicable Diseases ,Article ,03 medical and health sciences ,Response to treatment or vaccine ,Quantitative Trait, Heritable ,Genetics ,Genetic predisposition ,SNP ,MHC, major histocompatibility complex ,Animals ,Humans ,Genetic Predisposition to Disease ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Genetic Association Studies ,Genetic association ,VZV, Varicella Zooster virus ,HLA, human leukocyte antigen ,Immunity, Innate ,PRRSV, porcine reproductive and respiratory syndrome virus ,CC, Collaborative Cross ,030104 developmental biology ,HBV, hepatitis B virus ,Infectious disease (medical specialty) ,Expression quantitative trait loci ,Communicable Disease Control ,PCT, periodontal complex trait ,HIV-1, Human Immunodeficiency virus type 1 ,HCC, hepatocellular carcinoma ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
Genome-wide association studies (GWASs) have been widely applied to identify genetic factors that affect complex diseases or traits. Presently, the GWAS Catalog includes > 2800 human studies. Of these, only a minority have investigated the susceptibility to infectious diseases or the response to therapies for the treatment or prevention of infections. Despite their limited application in the field, GWASs have provided valuable insights by pinpointing associations to both innate and adaptive immune response loci, as well as novel unexpected risk factors for infection susceptibility. Herein, we discuss some issues and caveats of GWASs for infectious diseases, we review the most recent findings ensuing from these studies, and we provide a brief summary of selected GWASs for infections in non-human mammals. We conclude that, although the general trend in the field of complex traits is to shift from GWAS to next-generation sequencing, important knowledge on infectious disease-related traits can be still gained by GWASs, especially for those conditions that have never been investigated using this approach. We suggest that future studies will benefit from the leveraging of information from the host's and pathogen's genomes, as well as from the exploration of models that incorporate heterogeneity across populations and phenotypes. Interactions within HLA genes or among HLA variants and polymorphisms located outside the major histocompatibility complex may also play an important role in shaping the susceptibility and response to invading pathogens., Highlights • Relatively few GWASs for infectious diseases were performed. • Phenotype heterogeneity and case/control misclassification can affect GWAS power. • Adaptive and innate immunity loci were identified in several infectious disease GWASs. • Unexpected loci (e.g., lncRNAs) were also associated with infection susceptibility. • GWASs should integrate host and pathogen diversity and use complex association models.
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- 2017
22. A 6-amino acid insertion/deletion polymorphism in the mucin domain of TIM-1 confers protections against HIV-1 infection
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Micaela Garziano, Chiara Pontremoli, Jorge Sanchez, Manuela Sironi, Mara Biasin, María Teresa Rugeles, Francesca Vichi, Irma Saulle, Wbeimar Aguilar-Jimenez, Sergio Lo Caputo, Christian Brander, Samandhy Cedeño, Wildeman Zapata, Mario Clerici, Francesco Mazzotta, Diego Forni, Rachele Cagliani, Daria Trabattoni, and Stefania Riva
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Adult ,Male ,0301 basic medicine ,Immunology ,Human immunodeficiency virus (HIV) ,HIV Infections ,Colombia ,Virus Replication ,medicine.disease_cause ,Microbiology ,Cohort Studies ,Young Adult ,03 medical and health sciences ,Gene Frequency ,Peru ,Genotype ,medicine ,Humans ,Insertion deletion ,Hepatitis A Virus Cellular Receptor 1 ,Amino Acids ,Allele ,Gene ,Cells, Cultured ,Disease Resistance ,Sequence Deletion ,chemistry.chemical_classification ,Polymorphism, Genetic ,biology ,Mucin ,Middle Aged ,Thailand ,030112 virology ,Virology ,Amino acid ,Mutagenesis, Insertional ,030104 developmental biology ,Infectious Diseases ,Italy ,chemistry ,Case-Control Studies ,HIV-1 ,biology.protein ,Female ,Antibody - Abstract
We investigated whether a 6-amino acid insertion/deletion polymorphism in the mucin domain of TIM-1 (T-cell immunoglobulin and mucin domain 1), modulates susceptibility to HIV-1 infection. The polymorphism was genotyped in three case/control cohorts of HIV-1 exposed seronegative individuals (HESN) and HIV-1 infected subjects from Italy, Peru, and Colombia; data from a Thai population were retrieved from the literature. Across all cohorts, homozygosity for the short TIM-1 allele was more common in HESNs than in HIV-1 infected subjects. A meta-analysis of the four association analyses yielded a p value of 0.005. In vitro infection assays of CD4+ T lymphocytes indicated that homozygosity for the short allele is associated with lower rate of HIV-1 replication. These results suggest that the deletion allele protects from HIV-1 infection with a recessive effect.
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- 2017
23. The chameleonic genetics of Lassa virus
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Juan Carlos de la Torre and Manuela Sironi
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Genetics ,Lassa Fever ,Infectious Diseases ,Lassa virus ,medicine ,Animals ,Lizards ,Genomics ,Biology ,Liberia ,medicine.disease_cause ,Retrospective Studies - Published
- 2019
24. You Will Never Walk Alone: Codispersal of JC Polyomavirus with Human Populations
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Mario Clerici, Rachele Cagliani, Diego Forni, Uberto Pozzoli, and Manuela Sironi
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Gene Flow ,Mitochondrial DNA ,Remote Oceania ,Human Migration ,Philippines ,Population ,Oceania ,Taiwan ,Antarctic Regions ,Biology ,DNA, Mitochondrial ,Gene flow ,Evolution, Molecular ,Phylogenetics ,Genetics ,Humans ,Typing ,education ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,education.field_of_study ,Polyomavirus Infections ,Bayes Theorem ,JC Virus ,Phylogeography ,Evolutionary biology ,DNA, Viral ,Biological dispersal - Abstract
JC polyomavirus (JCPyV) is one of the most prevalent human viruses. Findings based on the geographic distribution of viral subtypes suggested that JCPyV codiverged with human populations. This view was however challenged by data reporting a much more recent origin and expansion of JCPyV. We collected information on ∼1,100 worldwide strains and we show that their geographic distribution roughly corresponds to major human migratory routes. Bayesian phylogeographic analysis inferred a Subsaharan origin for JCPyV, although with low posterior probability. High confidence inference at internal nodes provided strong support for a long-standing association between the virus and human populations. In line with these data, pairwise FST values for JCPyV and human mtDNA sampled from the same areas showed a positive and significant correlation. Likewise, very strong relationships were found when node ages in the JCPyV phylogeny were correlated with human population genetic distances (nuclear-marker based FST). Reconciliation analysis detected a significant cophylogenetic signal for the human population and JCPyV trees. Notably, JCPyV also traced some relatively recent migration events such as the expansion of people from the Philippines/Taiwan area into Remote Oceania, the gene flow between North-Eastern Siberian and Ainus, and the Koryak contribution to Circum-Arctic Americans. Finally, different molecular dating approaches dated the origin of JCPyV in a time frame that precedes human out-of-Africa migration. Thus, JCPyV infected early human populations and accompanied our species during worldwide dispersal. JCPyV typing can provide reliable geographic information and the virus most likely adapted to the genetic background of human populations.
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- 2019
25. ICTV Virus Taxonomy Profile: Arenaviridae
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Stephan Günther, Michael J. Buchmeier, Jean-Paul Gonzalez, J. Christopher S. Clegg, Sheli R. Radoshitzky, Jens H. Kuhn, Juan Carlos de la Torre, Víctor Romanowski, Rémi N. Charrel, Mark D. Stenglein, Manuela Sironi, Igor S. Lukashevich, Jussi Hepojoki, Maria S. Salvato, U.S. Army Medical Research Institute of Infectious Diseases, University of California, Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Les Mandinaux, 16450 Le Grand Madieu, Conditions et territoires d'émergence des maladies : dynamiques spatio-temporelles de l'émergence, évolution, diffusion/réduction des maladies, résistance et prémunition des hôtes (CTEM), Department of Virology, Bernhard Nocht Institute for Tropical Medicine - Bernhard-Nocht-Institut für Tropenmedizin [Hamburg, Germany] (BNITM), University of Helsinki, Institute of Veterinary Pathology, University of Zurich, Zurich, Switzerland, Integrated Research Facility at Fort Detrick (IRF-Frederick), National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), University of Louisville, Departamento de Ciencia y Tecnología [Buenos Aires], Universidad Nacional de Quilmes (UNQ), University of Maryland School of Medicine, University of Maryland System, Centro San Giovanni di Dio, Fatebenefratelli, Brescia (IRCCS), Università degli Studi di Brescia [Brescia], Colorado State University [Fort Collins] (CSU), The Scripps Research Institute [La Jolla], University of California [San Diego] (UC San Diego), University of California-University of California, U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), University of California (UC), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Università degli Studi di Brescia = University of Brescia (UniBs), The Scripps Research Institute [La Jolla, San Diego], and HAL AMU, Administrateur
- Subjects
0301 basic medicine ,viruses ,Arenaviridae ,[SDV]Life Sciences [q-bio] ,030106 microbiology ,Family Arenaviridae ,Genome, Viral ,Genome ,03 medical and health sciences ,Viral Proteins ,Viral genetics ,Phylogenetics ,Virology ,Animals ,Arenaviridae Infections ,Humans ,[SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology ,Virus classification ,Phylogeny ,ComputingMilieux_MISCELLANEOUS ,[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Arenavirus ,biology ,Fishes ,Reptiles ,biology.organism_classification ,[SDV] Life Sciences [q-bio] ,030104 developmental biology ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,RNA, Viral ,Mammarenavirus - Abstract
Members of the family Arenaviridae produce enveloped virions containing genomes consisting of two or three single-stranded RNA segments totalling about 10.5 kb. Arenaviruses can infect mammals, including humans and other primates, snakes, and fish. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Arenaviridae, which is available at www.ictv.global/report/arenaviridae.
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- 2019
26. RETRACTED: A complex evolutionary relationship between HHV-6A and HHV-6B
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Rachele Cagliani, Manuela Sironi, Mario Clerici, Diego Forni, and Uberto Pozzoli
- Subjects
0303 health sciences ,education.field_of_study ,Genetic diversity ,030306 microbiology ,viruses ,Population size ,Population ,virus diseases ,biochemical phenomena, metabolism, and nutrition ,Biology ,Disease cluster ,Microbiology ,Genome ,Nucleotide diversity ,03 medical and health sciences ,Evolutionary biology ,Virology ,Viral evolution ,education ,Recombination ,030304 developmental biology - Abstract
Human betaherpesviruses 6A and 6B (HHV-6A and HHV-6B) are highly prevalent in human populations. The genomes of these viruses can be stably integrated at the telomeres of human chromosomes and be vertically transmitted (inherited chromosomally integrated HHV-6, iciHHV6). We reconstructed the population structure of HHV-6 and we show that HHV-6A genomes diverged less than HHV-6B genomes from the ancestral common HHV-6A/B population. Analysis of ancestry proportions indicated that HHV-6A exogenous viruses and iciHHV-6A derived most of their genomes from distinct ancestral sources. Conversely, exogenous viral and iciHHV-6B populations were similar in terms of ancestry components, with no evident geographic structuring. Most HHV-6B genomes sampled to date derive from viral populations that experienced considerable drift. However, a population of HHV-6 exogenous viruses, currently classified as HHV-6B and sampled in New York state, formed a separate cluster (NY cluster) and harbored a considerable portion of HHV-6A-like ancestry. Recombination detection methods identified these viruses as interspecies recombinants, but phylogenetic reconstruction indicated that the recombination signals are due to shared ancestry. In analogy to iciHHV-6A, NY cluster viruses have high nucleotide diversity and constant population size. We propose that HHV-6A sequences and the NY cluster population diverged from an ancestral HHV-6A-like population. A relatively recent bottleneck of the NY (or a related) population with subsequent expansion originated most HHV-6B genomes currently sampled. Our findings indicate that the distinction between HHV-6A and -6B is not as clear-cut as previously thought. More generally, epidemiological and clinical surveys would benefit from taking HHV-6 genetic diversity into account.
- Published
- 2019
27. Possible European Origin of Circulating Varicella Zoster Virus Strains
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Mario Clerici, Chiara Pontremoli, Manuela Sironi, Diego Forni, and Rachele Cagliani
- Subjects
0301 basic medicine ,Chickenpox ,integumentary system ,viruses ,Varicella zoster virus ,virus diseases ,biochemical phenomena, metabolism, and nutrition ,Biology ,medicine.disease ,medicine.disease_cause ,Virology ,Genome ,eye diseases ,03 medical and health sciences ,Phylogeography ,030104 developmental biology ,0302 clinical medicine ,Infectious Diseases ,European origin ,Phylogenetics ,medicine ,Immunology and Allergy ,030212 general & internal medicine ,Clade ,Shingles - Abstract
Varicella zoster virus (VZV) is the causative agent of chickenpox and shingles. The geographic distribution of VZV clades was taken as evidence that VZV migrated out of Africa with human populations. We show that extant VZV strains most likely originated in Europe and not in Africa. Europe was also identified as the ancestral location for most internal nodes of the VZV phylogeny, including the ancestor of clade 5 strains. We also show that strains from clades 1, 2, 3, and 5 derived a major proportion of their ancestry from each of 4 ancestral populations. Conversely, viruses from other clades displayed variable levels of admixture. Some low-level admixture was also observed for clade 5 genomes, but only for non-African viruses. This pattern indicates that the clade 5 VZV strains do not represent recent introductions from Africa due to migratory fluxes. These data have also relevance for the definition and classification of VZV clades.
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- 2019
28. Taxonomy of the order Bunyavirales: second update 2018
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J. Christopher S. Clegg, Taiyun Wei, Sandra Junglen, Joseph L. DeRisi, F. Murilo Zerbini, Michele Digiaro, Xueping Zhou, R. O. Resende, Hideki Ebihara, Boris Klempa, Il-Ryong Choi, Jonas Klingström, Eric Bergeron, Anna Papa, Mark D. Stenglein, Scott Adkins, Rayapati A. Naidu, Xavier de Lamballerie, Shyi Dong Yeh, Víctor Romanowski, Massimo Turina, Koray Ergünay, Carol D. Blair, Anne Lise Haenni, Juan Carlos de la Torre, Matthew J. Ballinger, Yong-Zhen Zhang, Robert B. Tesh, Jens H. Kuhn, Amadou A. Sall, Nicole Mielke-Ehret, Charles H. Calisher, Martin Beer, Márcio Roberto Teixeira Nunes, Charles F. Fulhorst, Takahide Sasaya, Stanley A. Langevin, Giovanni P. Martelli, Aura R. Garrison, Roy A. Hall, Connie S. Schmaljohn, Holly R. Hughes, Rakesh K. Jain, Martin H. Groschup, Roger Hewson, Manuela Sironi, Clarence J. Peters, Anna E. Whitfield, Tatjana Avšič-Županc, Alexander Plyusnin, Felicity J. Burt, Rémi N. Charrel, Ali Mirazimi, Amy J. Lambert, Peter Simmonds, Michael J. Buchmeier, Toufic Elbeaino, Marco Marklewitz, Jean-Paul Gonzalez, Janusz T. Paweska, Jin Won Song, Xiǎohóng Shí, Igor S. Lukashevich, Hans Peter Mühlbach, Yukio Shirako, George Fú Gāo, Gustavo Palacios, Dennis A. Bente, Piet Maes, Richard Kormelink, Stephan Günther, Maria S. Salvato, S. V. Alkhovsky, Sheli R. Radoshitzky, Mike Drebot, Thomas Briese, Miranda Gilda Jonson, Jessica R. Spengler, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of Ljubljana, Institute of Diagnostic Virology (IVD), Friedrich-Loeffler-Institut (FLI), Fundación Instituto Leloir [Buenos Aires], Columbia Mailman School of Public Health, Columbia University [New York], Colorado State University [Fort Collins] (CSU), Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), International Rice Research Institute [Philippines] (IRRI), Consultative Group on International Agricultural Research [CGIAR] (CGIAR), The Scripps Research Institute [La Jolla, San Diego], Department of Biochemistry and Molecular Biology, University of Rochester [USA], Hacettepe University = Hacettepe Üniversitesi, The University of Texas Medical Branch (UTMB), Conditions et territoires d'émergence des maladies : dynamiques spatio-temporelles de l'émergence, évolution, diffusion/réduction des maladies, résistance et prémunition des hôtes (CTEM), Department of Virology, Bernhard Nocht Institute for Tropical Medicine - Bernhard-Nocht-Institut für Tropenmedizin [Hamburg, Germany] (BNITM), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Public Health England [Salisbury] (PHE), Humboldt State University (HSU), Slovak Academy of Science [Bratislava] (SAS), Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Laboratory of Virology [Wageningen], Wageningen University and Research [Wageningen] (WUR), Department of Systems Biology, Sandia National Laboratories, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Center for Microbiological Preparedness, Swedish Institute for Infectious Disease Control, Department of Arbovirology and Hemorrhagic Fevers, Instituto Evandro Chagas, U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Aristotle University of Thessaloniki, Department of Virology [Helsinki], Haartman Institute [Helsinki], Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Instituto de Biotecnología y Biología Molecular [La Plata] (IBBM), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET)-Facultad de Ciencias Exactas [La Plata], Universidad Nacional de la Plata [Argentine] (UNLP)-Universidad Nacional de la Plata [Argentine] (UNLP), Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP), Divison of Plant Protection, National Agricultural Research Center, National Agricultural Research Center, University of Edinburgh, Centro San Giovanni di Dio, Fatebenefratelli, Brescia (IRCCS), Università degli Studi di Brescia = University of Brescia (UniBs), Department of Pathology, University of Alabama at Birmingham [ Birmingham] (UAB), Southern Crop Protection and Food Research Centre, Agriculture and Agri-Food (AAFC), Universidade Federal de Viçosa = Federal University of Viçosa (UFV), State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong (HKU), National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Medical School, University of Ljubljana, Aix Marseille Université (AMU)-Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM), The Scripps Research Institute [La Jolla], University of California [San Diego] (UC San Diego), University of California-University of California, University of Bari Aldo Moro (UNIBA), Army Medical Research Institute of Infectious Diseases [USA] (USAMRIID), University of Helsinki-University of Helsinki-Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, U.S. Army Medical Research Institute of Infectious Diseases, Università degli Studi di Brescia [Brescia], Agriculture and Agri-Food [Ottawa] (AAFC), and Universidade Federal de Vicosa (UFV)
- Subjects
[SDV]Life Sciences [q-bio] ,Family Arenaviridae ,Laboratory of Virology ,cogovirus ,bunyavirus ,Biology ,Bunyaviridae / classifica??o ,Medical and Health Sciences ,Article ,Laboratorium voor Virologie ,ICTV ,03 medical and health sciences ,Tospovirus ,Virology ,Life Science ,Animals ,Humans ,Arenaviridae Infections ,Bunyavirales ,Arenaviridae ,ComputingMilieux_MISCELLANEOUS ,Phylogeny ,030304 developmental biology ,2. Zero hunger ,0303 health sciences ,Agricultural and Veterinary Sciences ,030306 microbiology ,General Medicine ,Biological Sciences ,Arenaviridae / classifica??o ,Arbovirus / classifica??o ,Genealogy ,humanities ,3. Good health ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,classification ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Taxonomy (biology) ,EPS - Abstract
This work was supported in part through Battelle Memorial Institute?s prime contract with the US National Institute of Allergy and Infectious Diseases (NIAID) under Contract No. HHSN272200700016I (J.H.K.). This work was also funded in part by National Institutes of Health (NIH) contract HHSN272201000040I/HHSN27200004/D04 and grant R24AI120942 (R.B.T.) Rega Institute. Infectious Diseases unit. Leuven, Leuven, Belgium. United States Department of Agriculture. Agricultural Research Service. US Horticultural Research Laboratory. Fort Pierce, FL, USA. Ministry of Health of the Russian Federation. N. F. Gamaleya Federal Research Center for Epidemiology and Microbiology. D. I. Ivanovsky Institute of Virology. Moscow, Russia. University of Ljubljana. Ljubljana Faculty of Medicine. Ljubljana, Slovenia. Mississippi State University. Department of Biological Sciences. Mississippi State, MS, USA. University of Texas Medical Branch. Galveston, TX, USA. Institute of Diagnostic Virology. Friedrich-Loefer-Institut. Greifswald-Insel Riems, Germany. Centers for Disease Control and Prevention. Division of High-Consequence Pathogens and Pathology. Viral Special Pathogens Branch. Atlanta, GA, USA. Colorado State University. Department of Microbiology. Immunology & Pathology, Arthropod-borne and Infectious Diseases Laboratory. Fort Collins, CO, USA. Columbia University. Center for Infection and Immunity. Department of Epidemiology, Mailman School of Public Health. New York, NY, USA. University of California. Department of Molecular Biology and Biochemistry. Irvine, CA, USA. National Health Laboratory Service. Division of Virology. Bloemfontein. Republic of South Africa / University of the Free State. Division of Virology. Bloemfontein, Republic of South Africa. Colorado State University. Department of Microbiology. Immunology & Pathology, Arthropod-borne and Infectious Diseases Laboratory. Fort Collins, CO, USA. Unit? des Virus Emergents (Aix-Marseille Univ?IRD 190? Inserm 1207?IHU M?diterran?e Infection). Marseille, France. International Rice Research Institute. Plant Breeding Genetics and Biotechnology Division. Los Ba?os, Philippines. Les MandinauxLe Grand Madieu. France. The Scripps Research Institute. Department of Immunology and Microbiology IMM-6. La Jolla, USA. Unit? des Virus Emergents (Aix-Marseille Univ?IRD 190?Inserm 1207?IHU M?diterran?e Infection). Marseille, France. University of California. Department of Medicine. San Francisco, USA / University of California. Department of Biochemistry and Biophysics. San Francisco, USA / University of California. Department of Microbiology. San Francisco, USA. Istituto Agronomico Mediterraneo di Bari. Valenzano, Italy. Public Health Agency of Canada. National Microbiology Laboratory. Zoonotic Diseases and Special Pathogens. Winnipeg, Canada. Mayo Clinic. Department of Molecular Medicine. Rochester, USA. Istituto Agronomico Mediterraneo di Bari. Valenzano, Italy. Hacettepe University. Faculty of Medicine. Department of Medical Microbiology. Virology Unit. Ankara, Turkey. University of Texas Medical Branch. Galveston, TX, USA. United States Army Medical Research Institute of Infectious Diseases. Fort Detrick, Frederick, USA. Chinese Center for Disease Control and Prevention. National Institute for Viral Disease Control and Prevention. Beijing, China. Kansas State University. Center of Excellence for Emerging and Zoonotic Animal Disease. Manhattan, USA. Chinese Center for Disease Control and Prevention. National Institute for Communicable Disease Control and Prevention. Beijing, China / Fudan University. Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences. Shanghai, China. WHO Collaborating Centre for Arboviruses and Hemorrhagic Fever Reference and Research. Bernhard-Nocht Institute for Tropical Medicine. Department of Virology. Hamburg, Germany. CNRS- Paris-Diderot. Institut Jacques Monod. Paris, France. The University of Queensland. School of Chemistry and Molecular Biosciences. Australian Infectious Diseases Research Centre. Brisbane, Australia. Public Health England. Salisbury, UK. Centers for Disease Control and Prevention. Fort Collins, USA. Indian Agricultural Research Institute. Division of Plant Pathology. New Delhi, India. Seoul National University. College of Agriculture and Life Sciences. Department of Agricultural Biotechnology, Center for Fungal Pathogenesis. Seoul, Korea. Humboldt-University Berlin, and Berlin Institute of Health. corporate member of Free University Berlin. Institute of Virology. Charit?-Universit?tsmedizin Berlin. Berlin, Germany / German Centre for Infection Research. Berlin, Germany. Humboldt-University Berlin, and Berlin Institute of Health. corporate member of Free University Berlin. Institute of Virology. Charit?-Universit?tsmedizin Berlin. Berlin, Germany / Slovak Academy of Sciences. Biomedical Research Center. Bratislava, Slovakia. Karolinska University Hospital. Center for Infectious Medicine, Karolinska Institutet. Department of Medicine Huddinge. Stockholm, Sweden. Wageningen University. Department of Plant Sciences. Laboratory of Virology. Wageningen, The Netherlands. Centers for Disease Control and Prevention. Fort Collins, USA. University of Washington. Department of Microbiology. Washington, USA. University of Louisville. School of Medicine. The Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases. Department of Pharmacology and Toxicology. Louisville, USA. Humboldt-University Berlin, and Berlin Institute of Health. corporate member of Free University Berlin. Institute of Virology. Charit?-Universit?tsmedizin Berlin. Berlin, Germany / German Centre for Infection Research. Berlin, Germany. University of Bari Aldo Moro. Department of Plant, Soil and Food Sciences. Bari, Italy. University of Hamburg. Biocentre Klein Flottbek. Hamburg, Germany. Folkhalsomyndigheten. Stockholm, Sweden. University of Hamburg. Biocentre Klein Flottbek. Hamburg, Germany. Washington State University. Irrigated Agricultural Research and Extension Center. Department of Plant Pathology. Prosser, USA. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Centro de Inova??es Tecnol?gicas. Ananindeua, PA, Brasil. United States Army Medical Research Institute of Infectious Diseases. Fort Detrick, Frederick, USA. Aristotle University of Thessaloniki. National Reference Centre for Arboviruses and Haemorrhagic Fever Viruses. Department of Microbiology, Medical School. Thessaloniki, Greece. National Health Laboratory Service. National Institute for Communicable Diseases. Centre for Emerging Zoonotic and Parasitic Diseases. Sandringham, South Africa / University of Pretoria. Centre for Viral Zoonoses, Faculty of Health Sciences. Department of Medical Virology. Pretoria South Africa. University of Texas Medical Branch. Galveston, TX, USA. University of Helsinki. Department of Virology. Medicum, Helsinki, Finland. United States Army Medical Research Institute of Infectious Diseases. Fort Detrick, Frederick, USA. Universidade de Bras?lia. Departamento de Biologia Celular. Bras?lia , DF, Brazil. Universidad Nacional de La Plata - Consejo Nacional de Investigaciones Cient?ficas y T?cnicas. Centro Cientifico Technol?gico-La Plata. Instituto de Biotecnolog?a y Biolog?a Molecular. La Plata, Argentina. Institut Pasteur de Dakar. Dakar, Senegal. University of Maryland School of Medicine. Institute of Human Virology. Baltimore, USA. National Agriculture and Food Research Organization. Department of Planning and Coordination. Tsukuba, Japan. United States Army Medical Research Institute of Infectious Diseases. Fort Detrick, Frederick, USA. MRC-University of Glasgow Centre for Virus Research. Glasgow, UK. University of Tokyo. Asian Center for Bioresources and Environmental Sciences. Tokyo, Japan. University of Oxford. Department of Medicine. Oxford, UK. Bioinformatics Scientific Institute IRCCS E. MEDEA. Bosisio Parini, Italy. Korea University. College of Medicine. Department of Microbiology. Seoul. Republic of Korea. Centers for Disease Control and Prevention. Division of High-Consequence Pathogens and Pathology. Viral Special Pathogens Branch. Atlanta, GA, USA. Colorado State University. Immunology and Pathology. Department of Microbiology. Fort Collins, USA. University of Texas Medical Branch. Galveston, TX, USA. CNR. Institute for Sustainable Plant Protection. Torino, Italy. Fujian Agriculture and Forestry University. Institute of Plant Virology. Fujian Province Key Laboratory of Plant Virology. Fuzhou, China. North Carolina State University. Department of Entomology and Plant Pathology. Raleigh, USA. National Chung Hsing University. Department of Plant Pathology. Taichung, Taiwan. Universidade Federal de Vi?osa. Departamento de Fitopatologia/BIOAGRO. Vi?osa, MG, Brazil. Chinese Center for Disease Control and Prevention. National Institute for Communicable Disease Control and Prevention. Beijing, China / Fudan University. Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences. Shanghai, China. Chinese Academy of Agricultural Sciences. Institute of Plant Protection. State Key Laboratory for Biology of Plant Diseases and Insect Pests. Beijing, China. National Institutes of Health (NIH). National Institute of Allergy and Infectious Diseases (NIAID). Division of Clinical Research (DCR). Integrated Research Facility at Fort Detrick (IRF-Frederick). Frederick, USA. In October 2018, the order Bunyavirales was amended by inclusion of the family Arenaviridae, abolishment of three families, creation of three new families, 19 new genera, and 14 new species, and renaming of three genera and 22 species. This article presents the updated taxonomy of the order Bunyavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV).
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- 2019
29. Phylogenies in ART: HIV reservoirs, HIV latency and drug resistance
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Andrea Gori, Mario Clerici, Manuela Sironi, and Alessandra Bandera
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0301 basic medicine ,Anti-HIV Agents ,Human immunodeficiency virus (HIV) ,Viremia ,HIV Infections ,Drug resistance ,Biology ,medicine.disease_cause ,030226 pharmacology & pharmacy ,03 medical and health sciences ,0302 clinical medicine ,Phylogenetics ,Antiretroviral Therapy, Highly Active ,Drug Discovery ,Virus latency ,Drug Resistance, Viral ,medicine ,Humans ,Latency (engineering) ,Phylogeny ,Pharmacology ,Mutation ,HIV ,medicine.disease ,Virology ,Virus Latency ,030104 developmental biology ,Viral load - Abstract
Combination antiretroviral therapy (ART) has significantly reduced the morbidity and mortality resulting from HIV infection. ART is, however, unable to eradicate HIV, which persists latently in several cell types and tissues. Phylogenetic analyses suggested that the proliferation of cells infected before ART initiation is mainly responsible for residual viremia, although controversy still exists. Conversely, it is widely accepted that drug resistance mutations (DRMs) do not appear during ART in patients with suppressed viral loads. Studies based on sequence clustering have in fact indicated that, at least in developed countries, HIV-infected ART-naive patients are the major source of drug-resistant viruses. Analysis of longitudinally sampled sequences have also shown that DRMs have variable fitness costs, which are strongly influenced by the viral genetic background.
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- 2019
30. Positive Selection Drives Evolution at the Host–Filovirus Interaction Surface
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Luca De Gioia, Diego Forni, Giulia Filippi, Uberto Pozzoli, Rachele Cagliani, Chiara Pontremoli, Mario Clerici, Manuela Sironi, Pontremoli, C, Forni, D, Cagliani, R, Filippi, G, De Gioia, L, Pozzoli, U, Clerici, M, and Sironi, M
- Subjects
0301 basic medicine ,Vesicular Transport Proteins ,medicine.disease_cause ,Bioinformatics ,Epitope ,Epitopes ,Ebolaviru ,Negative selection ,Viral Envelope Proteins ,hemic and lymphatic diseases ,Phylogeny ,Genetics ,Membrane Glycoproteins ,biology ,Viral Envelope Protein ,Ebolavirus ,Biological Evolution ,Host-Pathogen Interaction ,Host-Pathogen Interactions ,Membrane Glycoprotein ,Human ,congenital, hereditary, and neonatal diseases and abnormalities ,Host Specificity ,Evolution, Molecular ,03 medical and health sciences ,Vesicular Transport Protein ,Antigen ,positive selection ,Phylogenetics ,medicine ,Animals ,Humans ,Amino Acid Sequence ,Selection, Genetic ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,arm race ,Animal ,nutritional and metabolic diseases ,Filoviridae ,Marburgvirus ,biology.organism_classification ,NPC1 ,030104 developmental biology ,Adaptation ,Carrier Proteins ,Carrier Protein - Abstract
Filovirus infection is mediated by engagement of the surface-exposed glycoprotein (GP) by its cellular receptor, NPC1 (Niemann-Pick C1). Two loops in the C domain of NPC1 (NPC1-C) bind filovirus GP. Herein, we show that filovirus GP and NPC1-C evolve under mutual selective pressure. Analysis of a large mammalian phylogeny indicated that strong functional/structural constraints limit the NPC1 sequence space available for adaptive change and most sites at the contact interface with GP are under negative selection. These constraints notwithstanding, we detected positive selection at NPC1-C in all mammalian orders, from Primates to Xenarthra. Different codons evolved adaptively in distinct mammals, and most selected sites are located within the two NPC1-C loops that engage GP, or at their anchor points. In Homininae, NPC1-C was a preferential selection target, and the T419I variant possibly represents a human-specific adaptation to filovirus infection. On the other side of the arms-race, GP evolved adaptively during filovirus speciation. One of the selected sites (S142Q) establishes several atom-to-atom contacts with NPC1-C. Additional selected sites are located within epitopes recognized by neutralizing antibodies, including the 14G7 epitope, where sites selected during the recent EBOV epidemic also map. Finally, pairs of co-evolving sites in Marburgviruses and Ebolaviruses were found to involve antigenic determinants. These findings suggest that the host humoral immune response was a major selective pressure during filovirus speciation. The S142Q variant may contribute to determine Ebolavirus host range in the wild. If this were the case, EBOV/BDBV (S142) and SUDV (Q142) may not share the same reservoir(s).
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- 2016
31. Evolution and Genetic Diversity of Primate Cytomegaloviruses
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Alessandra Mozzi, Diego Forni, Rachele Cagliani, and Manuela Sironi
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0301 basic medicine ,Microbiology (medical) ,Human cytomegalovirus ,viruses ,030106 microbiology ,Review ,Biology ,medicine.disease_cause ,Microbiology ,Genome ,03 medical and health sciences ,positive selection ,Virology ,medicine ,Coding region ,genome organization ,species–specificity ,cytomegalovirus ,lcsh:QH301-705.5 ,Gene ,non–human primates ,Genomic organization ,Genetics ,Genetic diversity ,virus diseases ,Cytomegalovirus ,medicine.disease ,030104 developmental biology ,lcsh:Biology (General) ,Adaptation - Abstract
Cytomegaloviruses (CMVs) infect many mammals, including humans and non–human primates (NHPs). Human cytomegalovirus (HCMV) is an important opportunistic pathogen among immunocompromised patients and represents the most common infectious cause of birth defects. HCMV possesses a large genome and very high genetic diversity. NHP–infecting CMVs share with HCMV a similar genomic organization and coding content, as well as the course of viral infection. Recent technological advances have allowed the sequencing of several HCMV strains from clinical samples and provided insight into the diversity of NHP–infecting CMVs. The emerging picture indicates that, with the exclusion of core genes (genes that have orthologs in all herpesviruses), CMV genomes are relatively plastic and diverse in terms of gene content, both at the inter– and at the intra–species level. Such variability most likely underlies the strict species–specificity of these viruses, as well as their ability to persist lifelong and with relatively little damage to their hosts. However, core genes, despite their strong conservation, also represented a target of adaptive evolution and subtle changes in their coding sequence contributed to CMV adaptation to different hosts. Indubitably, important knowledge gaps remain, the most relevant of which concerns the role of viral genetics in HCMV–associated human disease.
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- 2020
32. Genetic conflicts with Plasmodium parasites and functional constraints shape the evolution of erythrocyte cytoskeletal proteins
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Diego Forni, Mario Clerici, Manuela Sironi, and Rachele Cagliani
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Primates ,0301 basic medicine ,Plasmodium ,Erythrocytes ,Adaptation, Biological ,Protozoan Proteins ,lcsh:Medicine ,Virulence ,KAHRP ,Biology ,Genome ,Article ,Evolution, Molecular ,03 medical and health sciences ,Negative selection ,ANK1 ,parasitic diseases ,Animals ,Humans ,Selection, Genetic ,lcsh:Science ,Gene ,Genetics ,Multidisciplinary ,lcsh:R ,biology.organism_classification ,Cytoskeletal Proteins ,030104 developmental biology ,lcsh:Q ,Adaptation - Abstract
Plasmodium parasites exerted a strong selective pressure on primate genomes and mutations in genes encoding erythrocyte cytoskeleton proteins (ECP) determine protective effects against Plasmodium infection/pathogenesis. We thus hypothesized that ECP-encoding genes have evolved in response to Plasmodium-driven selection. We analyzed the evolutionary history of 15 ECP-encoding genes in primates, as well as of their Plasmodium-encoded ligands (KAHRP, MESA and EMP3). Results indicated that EPB42, SLC4A1, and SPTA1 evolved under pervasive positive selection and that episodes of positive selection tended to occur more frequently in primate species that host a larger number of Plasmodium parasites. Conversely, several genes, including ANK1 and SPTB, displayed extensive signatures of purifying selection in primate phylogenies, Homininae lineages, and human populations, suggesting strong functional constraints. Analysis of Plasmodium genes indicated adaptive evolution in MESA and KAHRP; in the latter, different positively selected sites were located in the spectrin-binding domains. Because most of the positively selected sites in alpha-spectrin localized to the domains involved in the interaction with KAHRP, we suggest that the two proteins are engaged in an arms-race scenario. This observation is relevant because KAHRP is essential for the formation of “knobs”, which represent a major virulence determinant for P. falciparum.
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- 2018
33. The Diversity of Mammalian Hemoproteins and Microbial Heme Scavengers Is Shaped by an Arms Race for Iron Piracy
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Alessandra Mozzi, Diego Forni, Mario Clerici, Rachele Cagliani, and Manuela Sironi
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lcsh:Immunologic diseases. Allergy ,0301 basic medicine ,Staphylococcus aureus ,Hemeprotein ,iron piracy ,Iron ,Trypanosoma brucei brucei ,Immunology ,Protozoan Proteins ,Receptors, Cell Surface ,nutritional immunity ,Neisseria meningitidis ,Biology ,Trypanosoma brucei ,03 medical and health sciences ,chemistry.chemical_compound ,Bacterial Proteins ,positive selection ,Hemopexin ,Animals ,Humans ,Immunology and Allergy ,Cation Transport Proteins ,Heme ,Pathogen ,Gene ,Genetics ,Haptoglobins ,030102 biochemistry & molecular biology ,hemoglobin ,biology.organism_classification ,Haemophilus influenzae ,030104 developmental biology ,Lytic cycle ,chemistry ,Hemoglobin ,lcsh:RC581-607 - Abstract
Iron is an essential micronutrient for most living species. In mammals, hemoglobin (Hb) stores more than two thirds of the body's iron content. In the bloodstream, haptoglobin (Hp) and hemopexin (Hpx) sequester free Hb or heme. Pathogenic microorganisms usually acquire iron from their hosts and have evolved complex systems of iron piracy to circumvent nutritional immunity. Herein, we performed an evolutionary analysis of genes coding for mammalian heme-binding proteins and heme-scavengers in pathogen species. The underlying hypothesis is that these molecules are engaged in a molecular arms race. We show that positive selection drove the evolution of mammalian Hb and Hpx. Positively selected sites in Hb are located at the interaction surface with Neisseria meningitidis heme scavenger HpuA and with Staphylococcus aureus iron-regulated surface determinant B (IsdB). In turn, positively selected sites in HpuA and IsdB are located in the flexible protein regions that contact Hb. A residue in Hb (S45H) was also selected on the Caprinae branch. This site stabilizes the interaction with Trypanosoma brucei hemoglobin-haptoglobin (HbHp) receptor (TbHpHbR), a molecule that also mediates trypanosome lytic factor (TLF) entry. In TbHpHbR, positive selection drove the evolution of a variant (L210S) which allows evasion from TLF but reduces affinity for HbHp. Finally, selected sites in Hpx are located at the interaction surface with the Haemophilus influenzae hemophore HxuA, which in turn displays fast evolving sites at the Hpx-binding interface. These results shed light into host-pathogens conflicts and establish the importance of nutritional immunity as an evolutionary force.
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- 2018
34. Arenavirus genomics: novel insights into viral diversity, origin, and evolution
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Chiara Pontremoli, Manuela Sironi, and Diego Forni
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0301 basic medicine ,viruses ,Arenaviridae ,030106 microbiology ,Genomics ,Genome, Viral ,Biology ,medicine.disease_cause ,Genome ,Virus ,Evolution, Molecular ,03 medical and health sciences ,Virology ,Zoonoses ,medicine ,Animals ,Arenaviridae Infections ,Humans ,Evolutionary dynamics ,Arenavirus ,Host Microbial Interactions ,Fishes ,Genetic Variation ,High-Throughput Nucleotide Sequencing ,Reptiles ,biology.organism_classification ,030104 developmental biology ,Lassa virus ,Evolutionary biology ,Metagenomics - Abstract
Next-generation sequencing technologies have revolutionized our knowledge of virus diversity and evolution. In the case of arenaviruses, which are the focus of this review, metagenomic/metatranscriptomic approaches identified reptile-infecting and fish-infecting viruses, also showing that bi-segmented genomes are not a universal feature of the Arenaviridae family. Novel mammarenaviruses were described, allowing inference of their geographic origin and evolutionary dynamics. Extensive sequencing of Lassa virus (LASV) genomes revealed the zoonotic nature of most human infections and a Nigerian origin of LASV, which subsequently spread westward. Future efforts will likely identify many more arenaviruses and hopefully provide insight into the ultimate origin of the family, the pathogenic potential of its members, as well as the determinants of their geographic distribution.
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- 2018
35. Strategy of Human Cytomegalovirus To Escape Interferon Beta-Induced APOBEC3G Editing Activity
- Author
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Sara Pautasso, Diego Forni, Marisa Gariglio, Rachele Cagliani, Santo Landolfo, Marco De Andrea, Ganna Galitska, Manuela Sironi, Matteo Biolatti, and Valentina Dell'Oste
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0301 basic medicine ,Human cytomegalovirus ,Intrinsic immunity ,Male ,THP-1 Cells ,viruses ,Cytomegalovirus ,APOBEC-3G Deaminase ,Virus Replication ,Gene Knockout Techniques ,APOBEC3A ,APOBEC3G ,Effector ,gene editing ,virus diseases ,APOBEC3 ,3. Good health ,Virus-Cell Interactions ,Signal Transduction ,Immunology ,Foreskin ,Primary Cell Culture ,Genome, Viral ,Biology ,Microbiology ,Cell Line ,03 medical and health sciences ,Open Reading Frames ,Virology ,medicine ,Human Umbilical Vein Endothelial Cells ,Gene family ,Humans ,Gene ,APOBEC3, gene editing, human cytomegalovirus, immune evasion ,Immune Evasion ,Innate immune system ,Computational Biology ,Epithelial Cells ,Interferon-beta ,biochemical phenomena, metabolism, and nutrition ,Fibroblasts ,medicine.disease ,Immunity, Innate ,030104 developmental biology ,HEK293 Cells ,Gene Expression Regulation ,human cytomegalovirus ,Mutagenesis ,Insect Science ,CRISPR-Cas Systems - Abstract
The apolipoprotein B editing enzyme catalytic subunit 3 (APOBEC3) is a family of DNA cytosine deaminases that mutate and inactivate viral genomes by single-strand DNA editing, thus providing an innate immune response against a wide range of DNA and RNA viruses. In particular, APOBEC3A (A3A), a member of the APOBEC3 family, is induced by human cytomegalovirus (HCMV) in decidual tissues where it efficiently restricts HCMV replication, thereby acting as an intrinsic innate immune effector at the maternal-fetal interface. However, the widespread incidence of congenital HCMV infection implies that HCMV has evolved to counteract APOBEC3-induced mutagenesis through mechanisms that still remain to be fully established. Here, we have assessed gene expression and deaminase activity of various APOBEC3 gene family members in HCMV-infected primary human foreskin fibroblasts (HFFs). Specifically, we show that APOBEC3G (A3G) gene products and, to a lesser degree, those of A3F but not of A3A, are upregulated in HCMV-infected HFFs. We also show that HCMV-mediated induction of A3G expression is mediated by interferon beta (IFN-β), which is produced early during HCMV infection. However, knockout or overexpression of A3G does not affect HCMV replication, indicating that A3G is not a restriction factor for HCMV. Finally, through a bioinformatics approach, we show that HCMV has evolved mutational robustness against IFN-β by limiting the presence of A3G hot spots in essential open reading frames (ORFs) of its genome. Overall, our findings uncover a novel immune evasion strategy by HCMV with profound implications for HCMV infections. IMPORTANCE APOBEC3 family of proteins plays a pivotal role in intrinsic immunity defense mechanisms against multiple viral infections, including retroviruses, through the deamination activity. However, the currently available data on APOBEC3 editing mechanisms upon HCMV infection remain unclear. In the present study, we show that particularly the APOBEC3G (A3G) member of the deaminase family is strongly induced upon infection with HCMV in fibroblasts and that its upregulation is mediated by IFN-β. Furthermore, we were able to demonstrate that neither A3G knockout nor A3G overexpression appears to modulate HCMV replication, indicating that A3G does not inhibit HCMV replication. This may be explained by HCMV escape strategy from A3G activity through depletion of the preferred nucleotide motifs (hot spots) from its genome. The results may shed light on antiviral potential of APOBEC3 activity during HCMV infection, as well as the viral counteracting mechanisms under A3G-mediated selective pressure.
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- 2018
36. Multiple Selected Changes May Modulate the Molecular Interaction between Laverania RH5 and Primate Basigin
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Rachele Cagliani, Chiara Pontremoli, Diego Forni, Manuela Sironi, Uberto Pozzoli, and Mario Clerici
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0301 basic medicine ,Plasmodium ,Plasmodium falciparum ,Protozoan Proteins ,Microbiology ,Laverania ,Evolution, Molecular ,03 medical and health sciences ,Virology ,biology.animal ,Animals ,Humans ,Primate ,Selection, Genetic ,Letter to the Editor ,Binding Sites ,adaptive evolution ,biology ,Hominidae ,biology.organism_classification ,basigin ,QR1-502 ,Malaria ,Ape Diseases ,RH5 ,030104 developmental biology ,Evolutionary biology ,Basigin ,Protein Binding - Published
- 2018
37. Analysis of Reptarenavirus genomes indicates different selective forces acting on the S and L segments and recent expansion of common genotypes
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Chiara Pontremoli, Manuela Sironi, Diego Forni, and Rachele Cagliani
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0106 biological sciences ,0301 basic medicine ,Microbiology (medical) ,Models, Molecular ,Genes, Viral ,Genotype ,Protein Conformation ,Population ,Population genetics ,Genome, Viral ,010603 evolutionary biology ,01 natural sciences ,Microbiology ,Genome ,Nucleotide diversity ,03 medical and health sciences ,chemistry.chemical_compound ,Negative selection ,Open Reading Frames ,Structure-Activity Relationship ,Viral Proteins ,RNA polymerase ,Genetics ,Selection, Genetic ,education ,Arenaviridae ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Polymerase ,Phylogeny ,education.field_of_study ,biology ,Genetic Variation ,030104 developmental biology ,Infectious Diseases ,chemistry ,biology.protein - Abstract
Reptarenaviruses, a genus of snake-infecting viruses belonging to the family Arenaviridae, have bi-segmented genomes. The long (L) segment encodes the Z and L (RNA polymerase) proteins, whereas the short (S) segment codes for the glycoprotein precursor (GPC) and for the nucleoprotein (NP). Presently, reptarenaviruses have only been described in captive snakes. In these animals, mixed infections are common and most infected reptiles harbor multiple S and/or L segment genotypes. Within single animals, L segments are more genetically diverse than S segments and one S segment genotype (S6) was detected in the majority of snakes. Whether the unbalanced L to S segment ratio is due to stochastic events, to distinct replication/packaging efficiencies, or to differential selective pressure is presently unknown. We addressed these open questions by analyzing the ancient and recent evolutionary history of reptarenavirus genomes. Results indicated that purifying selection shaped the bulk of reptarenavirus coding sequences, although selective constraint was stronger for NP and L compared to GPC. During the divergence of reptarenavirus genomes, episodic positive selection contributed to the evolution of the viral polymerase, an observation that parallels those on mammarenaviruses. Population genetics analyses indicated that the most common S and L segment genotypes (including S6) display markedly negative Tajima's D values, but not low nucleotide diversity, suggesting recent population expansion. In conclusion, our data indicate that the selective pressures were stronger for the L segment than for the S segment, at least during reptarenavirus genotype divergence. More recently, the population sizes of some L and S segment genotypes expanded, suggesting that they out-competed the other genotypes, which show D values consistent with constant or decreasing population size. Competition among segments may have driven the disappearance of some S segment genotypes from wild and/or captive snake populations, eventually leading to the observed L to S imbalance.
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- 2018
38. Evolutionary Analysis Provides Insight Into the Origin and Adaptation of HCV
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Jacopo Vertemara, Chiara Pontremoli, Luca De Gioia, Manuela Sironi, Rachele Cagliani, Diego Forni, Uberto Pozzoli, Mario Clerici, Forni, D, Cagliani, R, Pontremoli, C, Pozzoli, U, Vertemara, J, Gioia, L, Clerici, M, and Sironi, M
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hepatitis C virus ,0301 basic medicine ,Microbiology (medical) ,Hepatitis C virus ,Hepacivirus ,030106 microbiology ,lcsh:QR1-502 ,HCV genotypes ,Human pathogen ,medicine.disease_cause ,Microbiology ,lcsh:Microbiology ,Virus ,law.invention ,03 medical and health sciences ,CD81 ,Equine hepaciviru ,law ,Genotype ,medicine ,TMRCA ,Original Research ,Genetics ,equine hepacivirus ,biology ,resistance-associated amino acid variants ,Transmission (medicine) ,Genetic heterogeneity ,Resistance-associated amino acid variant ,virus diseases ,Glires ,biology.organism_classification ,Phenotype ,digestive system diseases ,Positive selection ,030104 developmental biology ,Transmission (mechanics) ,Evolutionary biology ,Molecular dating ,Adaptation ,Hepatitis C viru - Abstract
Hepatitis C virus (HCV) belongs to the Hepacivirus genus and is genetically heterogeneous, with seven major genotypes further divided into several recognized subtypes. HCV origin was previously dated in a range between ∼200 and 1000 years ago. Hepaciviruses have been identified in several domestic and wild mammals, the largest viral diversity being observed in bats and rodents. The closest relatives of HCV were found in horses/donkeys (equine hepaciviruses, EHV). However, the origin of HCV as a human pathogen is still an unsolved puzzle. Using a selection-informed evolutionary model, we show that the common ancestor of extant HCV genotypes existed at least 3000 years ago (CI: 3192–5221 years ago), with the oldest genotypes being endemic to Asia. EHV originated around 1100 CE (CI: 291–1640 CE). These time estimates exclude that EHV transmission was mainly sustained by widespread veterinary practices and suggest that HCV originated from a single zoonotic event with subsequent diversification in human populations. We also describe a number of biologically important sites in the major HCV genotypes that have been positively selected and indicate that drug resistance-associated variants are significantly enriched at positively selected sites. HCV exploits several cell-surface molecules for cell entry, but only two of these (CD81 and OCLN) determine the species-specificity of infection. Herein evolutionary analyses do not support a long-standing association between primates and hepaciviruses, and signals of positive selection at CD81 were only observed in Chiroptera. No evidence of selection was detected for OCLN in any mammalian order. These results shed light on the origin of HCV and provide a catalog of candidate genetic modulators of HCV phenotypic diversity.
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- 2018
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39. Ancient Evolution of Mammarenaviruses: Adaptation via Changes in the L Protein and No Evidence for Host-Virus Codivergence
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Uberto Pozzoli, Mario Clerici, Rachele Cagliani, Diego Forni, Chiara Pontremoli, and Manuela Sironi
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0106 biological sciences ,0301 basic medicine ,Subfamily ,Old World ,Acclimatization ,010603 evolutionary biology ,01 natural sciences ,03 medical and health sciences ,Genus ,positive selection ,Genetics ,Animals ,Arenaviridae ,molecular dating ,Ecology, Evolution, Behavior and Systematics ,mammarenavirus ,biology ,Host (biology) ,Murinae ,biology.organism_classification ,Phylogeography ,030104 developmental biology ,Latin America ,Evolutionary biology ,Africa ,Host-Pathogen Interactions ,Adaptation ,Cricetidae ,Research Article - Abstract
The Mammarenavirus genus includes several pathogenic species of rodent-borne viruses. Old World (OW) mammarenaviruses infect rodents in the Murinae subfamily and are mainly transmitted in Africa and Asia; New World (NW) mammarenaviruses are found in rodents of the Cricetidae subfamily in the Americas. We applied a selection-informed method to estimate that OW and NW mammarenaviruses diverged less than ∼45,000 years ago (ya). By incorporating phylogeographic inference, we show that NW mammarenaviruses emerged in the Latin America-Caribbean region ∼41,400–3,300 ya, whereas OW mammarenaviruses originated ∼23,100–1,880 ya, most likely in Southern Africa. Cophylogenetic analysis indicated that cospeciation did not contribute significantly to mammarenavirus–host associations. Finally, we show that extremely strong selective pressure on the viral polymerase accompanied the speciation of NW viruses. These data suggest that the evolutionary history of mammarenaviruses was not driven by codivergence with their hosts. The viral polymerase should be regarded as a major determinant of mammarenavirus adaptation.
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- 2018
40. Positive selection underlies the species-specific binding ofPlasmodium falciparumRH5 to human basigin
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Rachele Cagliani, Chiara Pontremoli, Mario Clerici, Manuela Sironi, Uberto Pozzoli, and Diego Forni
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Lineage (genetic) ,Pan troglodytes ,Molecular Sequence Data ,Plasmodium falciparum ,Population ,Protozoan Proteins ,Antigens, Protozoan ,Laverania ,Evolution, Molecular ,Species Specificity ,Phylogenetics ,parasitic diseases ,Genetics ,Animals ,Humans ,Glycophorins ,Selection, Genetic ,education ,Gene ,Phylogeny ,Ecology, Evolution, Behavior and Systematics ,education.field_of_study ,Gorilla gorilla ,GYPA ,biology ,Sequence Analysis, DNA ,biology.organism_classification ,Genetics, Population ,Basigin ,Carrier Proteins ,Sequence Alignment ,Protein Binding - Abstract
Plasmodium falciparum, the causative agent of the deadliest form of malaria, is a member of the Laverania subgenus, which includes ape-infecting parasites. P. falciparum is thought to have originated in gorillas, although infection is now restricted to humans. Laverania parasites display remarkable host-specificity, which is partially mediated by the interaction between parasite ligands and host receptors. We analyse the evolution of BSG (basigin) and GYPA (glycophorin A) in primates/hominins, as well as of their Plasmodium-encoded ligands, PfRH5 and PfEBA175. We show that, in primates, positive selection targeted two sites in BSG (F27 and H102), both involved in PfRH5 binding. A population genetics-phylogenetics approach detected the strongest selection for the gorilla lineage: one of the positively selected sites (K191) is a major determinant of PfRH5 binding affinity. Analysis of RH5 genes indicated episodic selection on the P. falciparum branch; the positively selected W447 site is known to stabilize the interaction with human basigin. Conversely, we detect no selection in the receptor-binding region of EBA175 in the P. falciparum lineage. Its host receptor, GYPA, shows evidence of positive selection in all hominid lineages; selected codons include glycosylation sites that modulate PfEBA175 binding affinity. Data herein provide an evolutionary explanation for species-specific binding of the PfRH5-BSG ligand-receptor pair and support the hypothesis that positive selection at these genes drove the host shift leading to the emergence of P. falciparum as a human pathogen.
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- 2015
41. Natural Selection at the Brush-Border: Adaptations to Carbohydrate Diets in Humans and Other Mammals
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Alessandra Mozzi, Mario Clerici, Nereo Bresolin, Chiara Pontremoli, Manuela Sironi, Uberto Pozzoli, Giorgia Menozzi, Rachele Cagliani, Jacopo Vertemara, Diego Forni, Pontremoli, C, Mozzi, A, Forni, D, Cagliani, R, Pozzoli, U, Menozzi, G, Vertemara, J, Bresolin, N, Clerici, M, and Sironi, M
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Pan troglodytes ,Natural selection ,SLC2A2 ,Adaptation, Biological ,Carbohydrate metabolism ,Biology ,Mammal ,Sucrase-isomaltase complex ,alpha-Glucosidase ,Evolution, Molecular ,TREH ,Molecular evolution ,Dietary Carbohydrates ,Genetics ,Animals ,Humans ,SI ,Selection, Genetic ,Allele ,Domestication ,Gene ,Alleles ,Dietary Carbohydrate ,Ecology, Evolution, Behavior and Systematics ,Mammals ,Gorilla gorilla ,Microvilli ,Animal ,Pan troglodyte ,alpha-Glucosidases ,Ecology, Evolution, Behavior and Systematic ,Protein Structure, Tertiary ,Sucrase-Isomaltase Complex ,LCT ,Ancient DNA ,Carbohydrate Metabolism ,MGAM ,Research Article ,Human - Abstract
Dietary shifts can drive molecular evolution in mammals and a major transition in human history, the agricultural revolution, favored carbohydrate consumption. We investigated the evolutionary history of nine genes encoding brush-border proteins involved in carbohydrate digestion/absorption. Results indicated widespread adaptive evolution in mammals, with several branches experiencing episodic selection, particularly strong in bats. Many positively selected sites map to functional protein regions (e.g., within glucosidase catalytic crevices), with parallel evolution at SI (sucrase-isomaltase) and MGAM (maltase-glucoamylase). In human populations, five genes were targeted by positive selection acting on noncoding variants within regulatory elements. Analysis of ancient DNA samples indicated that most derived alleles were already present in the Paleolithic. Positively selected variants at SLC2A5 (fructose transporter) were an exception and possibly spread following the domestication of specific fruit crops. We conclude that agriculture determined no major selective event at carbohydrate metabolism genes in humans, with implications for susceptibility to metabolic disorders.
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- 2015
42. OASes and STING: Adaptive Evolution in Concert
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Diego Forni, Mario Clerici, Uberto Pozzoli, Nereo Bresolin, Chiara Pontremoli, Manuela Sironi, Rachele Cagliani, and Alessandra Mozzi
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Primates ,Pan troglodytes ,RNase P ,Population ,Biology ,RNase L ,Evolution, Molecular ,chemistry.chemical_compound ,positive selection ,Chiroptera ,Endoribonucleases ,2',5'-Oligoadenylate Synthetase ,Genetics ,Animals ,Humans ,Gene conversion ,education ,Gene ,Ecology, Evolution, Behavior and Systematics ,education.field_of_study ,Gorilla gorilla ,Membrane Proteins ,RNA ,Nucleotidyltransferases ,Protein Structure, Tertiary ,chemistry ,Stimulator of interferon genes ,Nucleic acid ,OAS ,DNA ,Research Article ,cGAS ,STING - Abstract
OAS (2'-5'-oligoadenylate synthases) proteins and cyclic GMP-AMP synthase (cGAS, gene symbol: MB21D1) patrol the cytoplasm for the presence of foreign nucleic acids. Upon binding to double-stranded RNA or double-stranded DNA, OAS proteins and cGAS produce nucleotide second messengers to activate RNase L and STING (stimulator of interferon genes, gene symbol: TMEM173), respectively; this leads to the initiation of antiviral responses. We analyzed the evolutionary history of the MB21D1-TMEM173 and OAS-RNASEL axes in primates and bats and found evidence of widespread positive selection in both orders. In TMEM173, residue 230, a major determinant of response to natural ligands and to mimetic drugs (e.g., DMXAA), was positively selected in Primates and Chiroptera. In both orders, selection also targeted an α-helix/loop element in RNase L that modulates the enzyme preference for single-stranded RNA versus stem loops. Analysis of positively selected sites in OAS1, OAS2, and MB21D1 revealed parallel evolution, with the corresponding residues being selected in different genes. As this cannot result from gene conversion, these data suggest that selective pressure acting on OAS and MB21D1 genes is related to nucleic acid recognition and to the specific mechanism of enzyme activation, which requires a conformational change. Finally, a population genetics-phylogenetics analysis in humans, chimpanzees, and gorillas detected several positively selected sites in most genes. Data herein shed light into species-specific differences in infection susceptibility and in response to synthetic compounds, with relevance for the design of synthetic compounds as vaccine adjuvants.
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- 2015
43. Evolutionary insights into host–pathogen interactions from mammalian sequence data
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Rachele Cagliani, Diego Forni, Manuela Sironi, and Mario Clerici
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Evolution ,Molecular Sequence Data ,Zoology ,Genomics ,Biology ,Article ,Data sequences ,Sequence Homology, Nucleic Acid ,Genetic variation ,Genetics ,Animals ,Humans ,Amino Acid Sequence ,Molecular Biology ,Pathogen ,Genetics (clinical) ,Mammals ,Genetic diversity ,Natural selection ,Base Sequence ,Sequence Homology, Amino Acid ,Human evolutionary genetics ,Host (biology) ,Comparative genomics ,Genetic Variation ,Sequence Analysis, DNA ,Biological Evolution ,Evolutionary biology ,Host-Pathogen Interactions ,Pathogens - Abstract
Key Points Infections are possibly the major selective pressure acting on humans, and host–pathogen interactions contribute to shaping the genetic diversity of both organisms.Comparisons among species provide a snapshot of selective events that have been unfolding over long timescales. These approaches use extant genetic diversity and phylogenetic relationships among species to identify positively selected sites.Positive selection often acts on a limited number of sites in a protein that is otherwise selectively constrained; one example is the localized signal of selection at Niemann–Pick C1 protein (NPC1), the receptor for the Ebola virus.As epitomized by the evolutionary history of tripartite motif-containing 5 (TRIM5), past infection events may leave a signature that affects the ability of extant species to fight emerging pathogens.Protein regions at the host–pathogen interface are expected to be targeted by the strongest selective pressure (this is the case for dipeptidyl peptidase 4 (DPP4) and angiotensin-converting enzyme 2 (ACE2), which act as receptors for coronaviruses).Other mammals host a wide range of viruses that are highly pathogenic for humans. Sequencing the genomes of these pathogens will be instrumental in refining our understanding of the process of host–pathogen interaction.Pathogen-driven natural selection is not limited to the immune system: genes that encode incidental pathogen receptors and components of the contact system and coagulation cascade can also be targeted. Supplementary information The online version of this article (doi:10.1038/nrg3905) contains supplementary material, which is available to authorized users., Host–pathogen interactions influence genetic diversity, and comparative genomic analyses are beginning to dissect genetic determinants involved in this process. This Review describes examples of such host–pathogen interactions and outline evolutionary approaches that are useful for identifying genomic regions associated with susceptibility to infection in mammals. Supplementary information The online version of this article (doi:10.1038/nrg3905) contains supplementary material, which is available to authorized users., Infections are one of the major selective pressures acting on humans, and host-pathogen interactions contribute to shaping the genetic diversity of both organisms. Evolutionary genomic studies take advantage of experiments that natural selection has been performing over millennia. In particular, inter-species comparative genomic analyses can highlight the genetic determinants of infection susceptibility or severity. Recent examples show how evolution-guided approaches can provide new insights into host–pathogen interactions, ultimately clarifying the basis of host range and explaining the emergence of different diseases. We describe the latest developments in comparative immunology and evolutionary genetics, showing their relevance for understanding the molecular determinants of infection susceptibility in mammals. Supplementary information The online version of this article (doi:10.1038/nrg3905) contains supplementary material, which is available to authorized users.
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- 2015
44. REST, a master regulator of neurogenesis, evolved under strong positive selection in humans and in non human primates
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Andrea Saul Costa, Diego Forni, Stefania Riva, Chiara Pontremoli, Monia Cabinio, Manuela Sironi, Mario Clerici, Francesca Baglio, Franca Rosa Guerini, Rachele Cagliani, Raffaello Nemni, and Alessandra Mozzi
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Primates ,0301 basic medicine ,Lineage (genetic) ,Neurogenesis ,lcsh:Medicine ,Gene Expression ,Biology ,Article ,Evolution, Molecular ,03 medical and health sciences ,Exon ,0302 clinical medicine ,medicine ,Animals ,Humans ,Amino Acids ,Selection, Genetic ,lcsh:Science ,Codon ,Transcription factor ,Gene ,Rest (music) ,Genetics ,Multidisciplinary ,lcsh:R ,Neurodegeneration ,Brain ,medicine.disease ,Repressor Proteins ,030104 developmental biology ,Gene Expression Regulation ,lcsh:Q ,Alzheimer's disease ,030217 neurology & neurosurgery - Abstract
The transcriptional repressor REST regulates many neuronal genes by binding RE1 motifs. About one third of human RE1s are recently evolved and specific to primates. As changes in the activity of a transcription factor reverberate on its downstream targets, we assessed whether REST displays fast evolutionary rates in primates. We show that REST was targeted by very strong positive selection during primate evolution. Positive selection was also evident in the human lineage, with six selected sites located in a region that surrounds a VNTR in exon 4. Analysis of expression data indicated that REST brain expression peaks during aging in humans but not in other primates. Because a REST coding variant (rs3796529) was previously associated with protection from hippocampal atrophy in elderly subjects with mild cognitive impairment (MCI), we analyzed a cohort of Alzheimer disease (AD) continuum patients. Genotyping of two coding variants (rs3796529 and rs2227902) located in the region surrounding the VNTR indicated a role for rs2227902 in modulation of hippocampal volume loss, indirectly confirming a role for REST in neuroprotection. Experimental studies will be instrumental to determine the functional effect of positively selected sites in REST and the role of REST variants in neuropreservation/neurodegeneration.
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- 2017
45. Distinct selective forces and Neanderthal introgression shaped genetic diversity at genes involved in neurodevelopmental disorders
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Uberto Pozzoli, Rachele Cagliani, Manuela Sironi, Mario Clerici, Alessandra Mozzi, and Diego Forni
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0301 basic medicine ,DYRK1A ,Science ,Introgression ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Article ,Evolution, Molecular ,03 medical and health sciences ,mental disorders ,medicine ,Animals ,Humans ,Genetic Predisposition to Disease ,Selection, Genetic ,Allele ,Gene ,Alleles ,Neanderthals ,Mammals ,Genetics ,Genetic diversity ,Multidisciplinary ,Natural selection ,Genetic Variation ,Hominidae ,medicine.disease ,030104 developmental biology ,Neurodevelopmental Disorders ,Autism spectrum disorder ,Medicine - Abstract
In addition to high intelligence, humans evolved specialized social-cognitive skills, which are specifically affected in children with autism spectrum disorder (ASD). Genes affected in ASD represent suitable candidates to study the evolution of human social cognition. We performed an evolutionary analysis on 68 genes associated to neurodevelopmental disorders; our data indicate that genetic diversity was shaped by distinct selective forces, including natural selection and introgression from archaic hominins. We discuss the possibility that segregation distortion during spermatogenesis accounts for a subset of ASD mutations. Finally, we detected modern-human-specific alleles in DYRK1A and TCF4. These variants are located within regions that display chromatin features typical of transcriptional enhancers in several brain areas, strongly suggesting a regulatory role. These SNPs thus represent candidates for association with neurodevelopmental disorders, and await experimental validation in future studies.
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- 2017
46. Susceptibility to type 2 diabetes may be modulated by haplotypes in G6PC2, a target of positive selection
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Stefania Riva, Nasser M. Al-Daghri, Rachele Cagliani, Majed S. Alokail, Chiara Pontremoli, Shaun Sabico, Manuela Sironi, Mario Clerici, Diego Forni, and Omar S. Al-Attas
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0106 biological sciences ,0301 basic medicine ,Adult ,Male ,G6PC2 ,Natural selection ,Saudi Arabia ,Single-nucleotide polymorphism ,Locus (genetics) ,Genome-wide association study ,Type 2 diabetes ,Association analysis ,Biology ,010603 evolutionary biology ,01 natural sciences ,Polymorphism, Single Nucleotide ,Evolution, Molecular ,03 medical and health sciences ,Negative selection ,Young Adult ,medicine ,Glucose homeostasis ,Animals ,Humans ,Gene ,Phylogeny ,Ecology, Evolution, Behavior and Systematics ,Aged ,Genetics ,Positive selection ,Haplotype ,Sequence Analysis, DNA ,Middle Aged ,medicine.disease ,Invertebrates ,030104 developmental biology ,Diabetes Mellitus, Type 2 ,Haplotypes ,Vertebrates ,Glucose-6-Phosphatase ,G6PC ,G6PC3 ,Female ,Research Article - Abstract
Background The endoplasmic reticulum enzyme glucose-6-phosphatase catalyzes the common terminal reaction in the gluconeogenic/glycogenolytic pathways and plays a central role in glucose homeostasis. In most mammals, different G6PC subunits are encoded by three paralogous genes (G6PC, G6PC2, and G6PC3). Mutations in G6PC and G6PC3 are responsible for human mendelian diseases, whereas variants in G6PC2 are associated with fasting glucose (FG) levels. Results We analyzed the evolutionary history of G6Pase genes. Results indicated that the three paralogs originated during early vertebrate evolution and that negative selection was the major force shaping diversity at these genes in mammals. Nonetheless, site-wise estimation of evolutionary rates at corresponding sites revealed weak correlations, suggesting that mammalian G6Pases have evolved different structural features over time. We also detected pervasive positive selection at mammalian G6PC2. Most selected residues localize in the C-terminal protein region, where several human variants associated with FG levels also map. This region was re-sequenced in ~560 subjects from Saudi Arabia, 185 of whom suffering from type 2 diabetes (T2D). The frequency of rare missense and nonsense variants was not significantly different in T2D and controls. Association analysis with two common missense variants (V219L and S342C) revealed a weak but significant association for both SNPs when analyses were conditioned on rs560887, previously identified in a GWAS for FG. Two haplotypes were significantly associated with T2D with an opposite effect direction. Conclusions We detected pervasive positive selection at mammalian G6PC2 genes and we suggest that distinct haplotypes at the G6PC2 locus modulate susceptibility to T2D. Electronic supplementary material The online version of this article (doi:10.1186/s12862-017-0897-z) contains supplementary material, which is available to authorized users.
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- 2017
47. Evolutionary analysis of Old World arenaviruses reveals a major adaptive contribution of the viral polymerase
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Rachele Cagliani, Stefania Riva, Diego Forni, Uberto Pozzoli, Mario Clerici, Ignacio G. Bravo, Chiara Pontremoli, Manuela Sironi, Centro San Giovanni di Dio, Fatebenefratelli, Brescia (IRCCS), Università degli Studi di Brescia [Brescia], Virostyle (MIVEGEC-Virostyle), Perturbations, Evolution, Virulence (PEV), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Department of Physiopatology and Transplantation, University of Milan (DEPT), and University of Milan
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0301 basic medicine ,viruses ,medicine.disease_cause ,Lymphocytic choriomeningitis ,Virus ,03 medical and health sciences ,Negative selection ,Viral Proteins ,Phylogenetics ,Genetics ,medicine ,Lymphocytic choriomeningitis virus ,Amino Acid Sequence ,Selection, Genetic ,Lassa virus ,Ecology, Evolution, Behavior and Systematics ,ComputingMilieux_MISCELLANEOUS ,Phylogeny ,Arenavirus ,biology ,[SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE] ,DNA-Directed RNA Polymerases ,medicine.disease ,biology.organism_classification ,Virology ,Biological Evolution ,Protein Structure, Tertiary ,Africa, Western ,030104 developmental biology ,Viral replication ,Viral evolution ,Arenaviruses, Old World - Abstract
The Old World (OW) arenavirus complex includes several species of rodent-borne viruses, some of which (i.e., Lassa virus, LASV and Lymphocytic choriomeningitis virus, LCMV) cause human diseases. Most LCMV and LASV infections are caused by rodent-to-human transmissions. Thus, viral evolution is largely determined by events that occur in the wildlife reservoirs. We used a set of human- and rodent-derived viral sequences to investigate the evolutionary history underlying OW arenavirus speciation, as well as the more recent selective events that accompanied LASV spread in West Africa. We show that the viral RNA polymerase (L protein) was a major positive selection target in OW arenaviruses and during LASV out-of-Nigeria migration. No evidence of selection was observed for the glycoprotein, whereas positive selection acted on the nucleoprotein (NP) during LCMV speciation. Positively selected sites in L and NP are surrounded by highly conserved residues, and the bulk of the viral genome evolves under purifying selection. Several positively selected sites are likely to modulate viral replication/transcription. In both L and NP, structural features (solvent exposed surface area) are important determinants of site-wise evolutionary rate variation. By incorporating several rodent-derived sequences, we also performed an analysis of OW arenavirus codon adaptation to the human host. Results do not support a previously hypothesized role of codon adaptation in disease severity for non-Nigerian strains. In conclusion, L and NP represent the major selection targets and possible determinants of disease presentation; these results suggest that field surveys and experimental studies should primarily focus on these proteins.
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- 2017
48. A common genetic variant in FOXP2 is associated with language-based learning (dis)abilities: Evidence from two Italian independent samples
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Alessandra Mozzi, Massimo Molteni, Stefania Riva, Valentina Riva, Diego Forni, Cecilia Marino, Rachele Cagliani, Sara Mascheretti, Franca Rosa Guerini, Mario Clerici, and Manuela Sironi
- Subjects
0301 basic medicine ,Genetics ,education.field_of_study ,Population ,Neuropsychology ,FOXP2 ,Biology ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Psychiatry and Mental health ,Fluency ,030104 developmental biology ,0302 clinical medicine ,Cohort ,Genetic model ,Allele ,education ,030217 neurology & neurosurgery ,Genetics (clinical) ,Genetic association - Abstract
Language-based Learning Disabilities (LLDs) encompass a group of complex, comorbid, and developmentally associated deficits in communication. Language impairment and developmental dyslexia (DD) represent the most recognized forms of LLDs. Substantial genetic correlations exist between language and reading (dis)abilities. Common variants in the FOXP2 gene were consistently associated with language- and reading-related neuropsychological and neuroanatomical phenotypes. We tested the effect of a FOXP2 common variant, that is, rs6980093 (A/G), on quantitative measures of language and reading in two independent Italian samples: a population-based cohort of 699 subjects (3-11 years old) and a sample of 572 children with DD (6-18 years old). rs6980093 modulates expressive language in the general population sample, with an effect on fluency scores. In the DD sample, the variant showed an association with the accuracy in the single word reading task. rs6980093 shows distinct genetic models of association in the two cohorts, with a dominant effect of the G allele in the general population sample and heterozygote advantage in the DD cohort. We provide preliminary evidence that rs6980093 associates with language and reading (dis)abilities in two independent Italian cohorts. rs6980093 is an intronic SNP, suggesting that it (or a linked variant) modulates phenotypic association via regulation of FOXP2 expression. Because FOXP2 brain expression is finely regulated, both temporally and spatially, it is possible that the two alleles at rs6980093 differentially modulate expression levels in a developmental stage- or brain area-specific manner. This might help explaining the heterozygote advantage effect and the different genetic models in the two cohorts.
- Published
- 2017
49. Albuminoid Genes: Evolving at the Interface of Dispensability and Selection
- Author
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Nereo Bresolin, Jacopo Vertemara, Manuela Sironi, Alessandra Mozzi, Uberto Pozzoli, Rachele Cagliani, Diego Forni, Mozzi, A, Forni, D, Cagliani, R, Pozzoli, U, Vertemara, J, Bresolin, N, and Sironi, M
- Subjects
Linkage disequilibrium ,Pan troglodytes ,vitamin D-binding protein ,Prostaglandin ,Vitamin D-binding protein ,Population ,Serum albumin ,Serum Albumin, Human ,vitamin D ,Plasma protein binding ,Linkage Disequilibrium ,Evolution, Molecular ,Negative selection ,positive selection ,Hibernation ,Haplotype ,Genetics ,Animals ,Humans ,Gene family ,alpha-Fetoprotein ,Selection, Genetic ,education ,Gene ,Serum Albumin ,albumin ,Ecology, Evolution, Behavior and Systematics ,education.field_of_study ,Binding Sites ,biology ,Animal ,Medicine (all) ,Pan troglodyte ,Fatty Acids ,Binding Site ,Ecology, Evolution, Behavior and Systematic ,Adaptation, Physiological ,Thyroxine ,Haplotypes ,Prostaglandins ,biology.protein ,Albuminoid ,alpha-Fetoproteins ,Fatty Acid ,Human ,Protein Binding ,Research Article ,albuminoids - Abstract
The albuminoid gene family comprises vitamin D-binding protein (GC), alpha-fetoprotein (AFP), afamin (AFM), and albumin (ALB). Albumin is the most abundant human serum protein, and, as the other family members, acts as a transporter of endogenous and exogenous substances including thyroxine, fatty acids, and drugs. Instead, the major cargo of GC is 25-hydroxyvitamin D. We performed an evolutionary study of albuminoid genes and we show that ALB evolved adaptively in mammals. Most positively selected sites are located within albumin-binding sites for fatty acids and thyroxine, as well as at the contact surface with neonatal Fc receptor. Positive selection was also detected for residues forming the prostaglandin-binding pocket. Adaptation to hibernation/torpor might explain the signatures of episodic positive selection we detected for few mammalian lineages. Application of a population genetics–phylogenetics approach showed that purifying selection represented a major force acting on albuminoid genes in both humans and chimpanzees, with the strongest constraint observed for human GC. Population genetic analysis revealed that GC was also the target of locally exerted selective pressure, which drove the frequency increase of different haplotypes in distinct human populations. A search for known variants that modulate GC and 25-hydroxyvitamin D concentrations revealed linkage disequilibrium with positively selected variants, although European and Asian major GC haplotypes carry alleles with reported opposite effect on GC concentration. Data herein indicate that albumin, an extremely abundant housekeeping protein, was the target of pervasive and episodic selection in mammals, whereas GC represented a selection target during the recent evolution of human populations.
- Published
- 2014
50. Human genome variability, natural selection and infectious diseases
- Author
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Manuela Sironi and Matteo Fumagalli
- Subjects
Genetics ,Genetic diversity ,education.field_of_study ,Natural selection ,Genome, Human ,Immunology ,Population ,Genetic Variation ,Biology ,Infections ,Genome ,Molecular evolution ,Evolutionary biology ,Genetic variation ,Animals ,Humans ,Immunology and Allergy ,Human genome ,Selection, Genetic ,education ,Selection (genetic algorithm) - Abstract
The recent availability of large-scale sequencing DNA data allowed researchers to investigate how genomic variation is distributed among populations. While demographic factors explain genome-wide population genetic diversity levels, scans for signatures of natural selection pinpointed several regions under non-neutral evolution. Recent studies found an enrichment of immune-related genes subjected to natural selection, suggesting that pathogens and infectious diseases have imposed a strong selective pressure throughout human history. Pathogen-mediated selection often targeted regulatory sites of genes belonging to the same biological pathway. Results from these studies have the potential to identify mutations that modulate infection susceptibility by integrating a population genomic approach with molecular immunology data and large-scale functional annotations.
- Published
- 2014
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