191 results on '"Roger Hewson"'
Search Results
2. Climate change and infectious disease: A prologue on multidisciplinary cooperation and predictive analytics
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Kenneth B. Yeh, Falgunee K. Parekh, Illich Mombo, Joseph Leimer, Roger Hewson, Gene Olinger, Jeanne M. Fair, Yijun Sun, and John Hay
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Public Health, Environmental and Occupational Health - Abstract
Climate change impacts global ecosystems at the interface of infectious disease agents and hosts and vectors for animals, humans, and plants. The climate is changing, and the impacts are complex, with multifaceted effects. In addition to connecting climate change and infectious diseases, we aim to draw attention to the challenges of working across multiple disciplines. Doing this requires concentrated efforts in a variety of areas to advance the technological state of the art and at the same time implement ideas and explain to the everyday citizen what is happening. The world's experience with COVID-19 has revealed many gaps in our past approaches to anticipating emerging infectious diseases. Most approaches to predicting outbreaks and identifying emerging microbes of major consequence have been with those causing high morbidity and mortality in humans and animals. These lagging indicators offer limited ability to prevent disease spillover and amplifications in new hosts. Leading indicators and novel approaches are more valuable and now feasible, with multidisciplinary approaches also within our grasp to provide links to disease predictions through holistic monitoring of micro and macro ecological changes. In this commentary, we describe niches for climate change and infectious diseases as well as overarching themes for the important role of collaborative team science, predictive analytics, and biosecurity. With a multidisciplinary cooperative “all call,” we can enhance our ability to engage and resolve current and emerging problems.
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- 2023
3. Monte Carlo modelling of an x-ray chamber for providing inactivation exposures to viruses
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Babak Afrough, Jonathan Eakins, and Roger Hewson
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Materials science ,X-Rays ,Monte Carlo method ,Public Health, Environmental and Occupational Health ,X-ray ,Analytical chemistry ,chemistry.chemical_element ,Refrigeration ,General Medicine ,Radiography ,chemistry ,Aluminium ,Viruses ,Dry ice ,Dosimetry ,Irradiation ,Radiometry ,Monte Carlo Method ,Waste Management and Disposal ,Beam (structure) - Abstract
The Monte Carlo radiation transport code MCNP6 has been used to model dosimetry for biological pathogen samples placed within a MultiRad 225 irradiation chamber, in order to inform virus deactivation protocols. Full characterisations of the photon spectra generated by the chamber’s x-ray tube were achieved for both 190 and 220 kV potentials, with and without aluminium and copper beam filters of different thicknesses. Dose rate maps to air and water within the chamber were then derived, along with corresponding conversion coefficient data. The maps were determined for samples located both on a shelf and on a dry ice refrigeration chamber, at different distances from the source. The potential depth-dose profiles through samples were also investigated. The optimum choice of filter for use in virus inactivation procedures will rely on a compromise between dose homogeneity and dose rate.
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- 2021
4. Identification of novel orthonairoviruses from rodents and shrews in Gabon, Central Africa
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Takehiro Ozeki, Haruka Abe, Yuri Ushijima, Chimène Nze-Nkogue, Etienne F. Akomo-Okoue, Ghislain W.E. Ella, Lilian B.M. Koumba, Branly C.B.B. Nso, Rodrigue Mintsa-Nguema, Patrice Makouloutou-Nzassi, Boris K. Makanga, Fred L.M. Nguelet, Georgelin N. Ondo, Marien J.V.M. Mbadinga, Yui Igasaki, Sayaka Okada, Minato Hirano, Kentaro Yoshii, Bertrand Lell, Laura C. Bonney, Roger Hewson, Yohei Kurosaki, and Jiro Yasuda
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Shrews ,Rodentia ,Orthonairovirus ,novel virus ,small mammals ,Virology ,Viruses ,surveillance ,Animals ,RNA ,virus screening ,Gabon ,Interferons ,Phylogeny ,Peptide Hydrolases - Abstract
In Africa, several emerging zoonotic viruses have been transmitted from small mammals such as rodents and shrews to humans. Although no clinical cases of small mammal-borne viral diseases have been reported in Central Africa, potential zoonotic viruses have been identified in rodents in the region. Therefore, we hypothesized that there may be unrecognized zoonotic viruses circulating in small mammals in Central Africa. Here, we investigated viruses that have been maintained among wild small mammals in Gabon to understand their potential risks to humans. We identified novel orthonairoviruses in 24.6 % of captured rodents and shrews from their kidney total RNA samples. Phylogenetic analysis revealed that the novel viruses, Lamusara virus (LMSV) and Lamgora virus, were closely related to Erve virus, which was previously identified in shrews of the genus Crocidura and has been suspected to cause neuropathogenic diseases in humans. Moreover, we show that the LMSV ovarian tumour domain protease, one of the virulence determination factors of orthonairoviruses, suppressed interferon signalling in human cells, suggesting the possible human pathogenicity of this virus. Taken together, our study demonstrates the presence of novel orthonairoviruses that may pose unrecognized risks of viral disease transmission in Gabon., The Journal of general virology, 103(10), art. no. 001796; 2022
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- 2022
5. Development of a cost-effective ovine antibody-based therapy against SARS-CoV-2 infection and contribution of antibodies specific to the spike subunit proteins
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Stephen Findlay-Wilson, Linda Easterbrook, Sandra Smith, Neville Pope, Gareth Humphries, Holger Schuhmann, Didier Ngabo, Emma Rayner, Ashley David Otter, Tom Coleman, Bethany Hicks, Victoria Anne Graham, Rachel Halkerston, Kostis Apostolakis, Stephen Taylor, Susan Fotheringham, Amanda Horton, Julia Anne Tree, Matthew Wand, Roger Hewson, and Stuart David Dowall
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Pharmacology ,Sheep ,SARS-CoV-2 ,Cost-Benefit Analysis ,Virology ,Spike Glycoprotein, Coronavirus ,Immunization, Passive ,Animals ,COVID-19 ,Antibodies, Viral ,Antibodies, Neutralizing ,COVID-19 Serotherapy ,COVID-19 Drug Treatment - Abstract
Antibodies against SARS-CoV-2 are important to generate protective immunity, with convalescent plasma one of the first therapies approved. An alternative source of polyclonal antibodies suitable for upscaling would be more amendable to regulatory approval and widespread use. In this study, sheep were immunised with SARS-CoV-2 whole spike protein or one of the subunit proteins: S1 and S2. Once substantial antibody titres were generated, plasma was collected and samples pooled for each antigen. Non-specific antibodies were removed via affinity-purification to yield candidate products for testing in a hamster model of SARS-CoV-2 infection. Affinity-purified polyclonal antibodies to whole spike, S1 and S2 proteins were evaluated for in vitro for neutralising activity against SARS-CoV-2 Wuhan-like virus (Australia/VIC01/2020) and a recent variant of concern, B.1.1.529 BA.1 (Omicron), antibody-binding, complement fixation and phagocytosis assays were also performed. All antibody preparations demonstrated an effect against SARS-CoV-2 disease in the hamster model of challenge, with those raised against the S2 subunit providing the most promise. A rapid, cost-effective therapy for COVID-19 was developed which provides a source of highly active immunoglobulin specific to SARS-CoV-2 with multi-functional activity.
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- 2022
6. Activity of a Carbohydrate-Binding Module Therapy, Neumifil, against SARS-CoV-2 Disease in a Hamster Model of Infection
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Rachel Fell, Jane A. Potter, Samantha Yuille, Franscisco J. Salguero, Robert Watson, Didier Ngabo, Karen Gooch, Roger Hewson, David Howat, and Stuart Dowall
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Infectious Diseases ,SARS-CoV-2 ,Cricetinae ,COVID-19 ,therapy ,host targeted ,Virology ,Spike Glycoprotein, Coronavirus ,Carbohydrates ,Humans ,Peptidyl-Dipeptidase A ,COVID-19 Drug Treatment - Abstract
The rapid global spread of severe acute respiratory coronavirus 2 (SARS-CoV-2) has resulted in an urgent effort to find efficacious therapeutics. Broad-spectrum therapies which could be used for other respiratory pathogens confer advantages, as do those based on targeting host cells that are not prone to the development of resistance by the pathogen. We tested an intranasally delivered carbohydrate-binding module (CBM) therapy, termed Neumifil, which is based on a CBM that has previously been shown to offer protection against the influenza virus through the binding of sialic acid receptors. Using the recognised hamster model of SARS-CoV-2 infection, we demonstrate that Neumifil significantly reduces clinical disease severity and pathological changes in the nasal cavity. Furthermore, we demonstrate Neumifil binding to the human angiotensin-converting enzyme 2 (ACE2) receptor and spike protein of SARS-CoV-2. This is the first report describing the testing of this type of broad-spectrum antiviral therapy in vivo and provides evidence for the advancement of Neumifil in further preclinical and clinical studies.
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- 2022
7. 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
- Published
- 2020
8. Adenoviral vectored vaccination protects against Crimean-Congo Haemorrhagic Fever disease in a lethal challenge model
- Author
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Jack E. Saunders, Ciaran Gilbride, Stuart Dowall, Susan Morris, Marta Ulaszewska, Alexandra J. Spencer, Emma Rayner, Victoria A. Graham, Emma Kennedy, Kelly Thomas, Roger Hewson, Sarah C. Gilbert, Sandra Belij-Rammerstorfer, and Teresa Lambe
- Subjects
General Medicine ,General Biochemistry, Genetics and Molecular Biology - Published
- 2023
9. X-ray inactivation of RNA viruses without loss of biological characteristics
- Author
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Kuiama Lewandowski, Daniel P. Carter, Victoria A. Graham, Jonathan Eakins, Stephen Findlay-Wilson, Sarah Durley-White, Babak Afrough, Roger Hewson, and Stuart D. Dowall
- Subjects
0301 basic medicine ,Outbreak response ,Science ,Computational biology ,Microbiology ,Viral Zoonoses ,Article ,03 medical and health sciences ,Biosafety ,Flaviviridae ,0302 clinical medicine ,Nairoviridae ,Chlorocebus aethiops ,Togaviridae ,Animals ,Humans ,RNA Viruses ,030212 general & internal medicine ,Vero Cells ,Multidisciplinary ,biology ,Sequence Analysis, RNA ,X-Rays ,Biological techniques ,RNA ,Civil Defense ,Feeder Cells ,Zika Virus ,Containment of Biohazards ,biology.organism_classification ,030104 developmental biology ,Phenuiviridae ,Nairovirus ,RNA, Viral ,Virus Inactivation ,Medicine ,Monte Carlo Method - Abstract
In the event of an unpredictable viral outbreak requiring high/maximum biosafety containment facilities (i.e. BSL3 and BSL4), X-ray irradiation has the potential to relieve pressures on conventional diagnostic bottlenecks and expediate work at lower containment. Guided by Monte Carlo modelling and in vitro 1-log10 decimal-reduction value (D-value) predictions, the X-ray photon energies required for the effective inactivation of zoonotic viruses belonging to the medically important families of Flaviviridae, Nairoviridae, Phenuiviridae and Togaviridae are demonstrated. Specifically, it is shown that an optimized irradiation approach is attractive for use in a multitude of downstream detection and functional assays, as it preserves key biochemical and immunological properties. This study provides evidence that X-ray irradiation can support emergency preparedness, outbreak response and front-line diagnostics in a safe, reproducible and scalable manner pertinent to operations that are otherwise restricted to higher containment BSL3 or BSL4 laboratories.
- Published
- 2020
10. Multi-omics insights into host-viral response and pathogenesis in Crimean-Congo hemorrhagic fever viruses for novel therapeutic target
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Akhil C. Banerjea, Ujjwal Neogi, Friedemann Weber, Anoop T. Ambikan, Stuart D. Dowall, Emma Kennedy, Vanessa Monteil, Rui Benfeitas, Nazif Elaldi, Sara Svensson-Akusjärvi, Roger Hewson, Jimmy Esneider Rodriguez, Ali Mirazimi, Ákos Végvári, Binnur Bagci, Soham Gupta, Sofia Appelberg, and Sağlık Bilimleri Fakültesi
- Subjects
Viral pathogenesis ,Systems biology ,Quantitative proteomics ,Biology ,Proteomics ,Antiviral Agents ,Immune system ,Cross-Sectional Studies ,Viral replication ,Interferon ,Immunology ,Hemorrhagic Fever Virus, Crimean-Congo ,medicine ,Leukocytes, Mononuclear ,Humans ,Hemorrhagic Fever, Crimean ,Interferons ,PI3K/AKT/mTOR pathway ,medicine.drug - Abstract
The pathogenesis and host-viral interactions of the Crimean-Congo hemorrhagic fever orthonairovirus (CCHFV) are convoluted and not well evaluated. Application of the multi-omics system biology approaches, including biological network analysis in elucidating the complex host-viral response, interrogates the viral pathogenesis. The present study aimed to fingerprint the system-level alterations during acute CCHFV-infection and the cellular immune responses during productive CCHFV-replication in vitro. We used system-wide network-based system biology analysis of peripheral blood mononuclear cells (PBMCs) from a longitudinal cohort of CCHF patients during the acute phase of infection and after one year of recovery (convalescent phase) followed by untargeted quantitative proteomics analysis of the most permissive CCHFV-infected Huh7 and SW13 cells. In the RNAseq analysis of the PBMCs, comparing the acute and convalescent-phase, we observed system-level host's metabolic reprogramming towards central carbon and energy metabolism (CCEM) with distinct upregulation of oxidative phosphorylation (OXPHOS) during CCHFV-infection. Upon application of network-based system biology methods, negative coordination of the biological signaling systems like FOXO/Notch axis and Akt/mTOR/HIF-1 signaling with metabolic pathways during CCHFV-infection were observed. The temporal quantitative proteomics in Huh7 showed a dynamic change in the CCEM over time and concordant with the cross-sectional proteomics in SW13 cells. By blocking the two key CCEM pathways, glycolysis and glutaminolysis, viral replication was inhibited in vitro. Activation of key interferon stimulating genes during infection suggested the role of type I and II interferon-mediated antiviral mechanisms both at the system level and during progressive replication.Crimean-Congo hemorrhagic fever (CCHF) is an emerging disease that is increasingly spreading to new populations. The condition is now endemic in almost 30 countries in sub-Saharan Africa, South-Eastern Europe, the Middle East and Central Asia. CCHF is caused by a tick-borne virus and can cause uncontrolled bleeding. It has a mortality rate of up to 40%, and there are currently no vaccines or effective treatments available. All viruses depend entirely on their hosts for reproduction, and they achieve this through hijacking the molecular machinery of the cells they infect. However, little is known about how the CCHF virus does this and how the cells respond. To understand more about the relationship between the cell’s metabolism and viral replication, Neogi, Elaldi et al. studied immune cells taken from patients during an infection and one year later. The gene activity of the cells showed that the virus prefers to hijack processes known as central carbon and energy metabolism. These are the main regulator of the cellular energy supply and the production of essential chemicals. By using cancer drugs to block these key pathways, Neogi, Elaldi et al. could reduce the viral reproduction in laboratory cells. These findings provide a clearer understanding of how the CCHF virus replicates inside human cells. By interfering with these processes, researchers could develop new antiviral strategies to treat the disease. One of the cancer drugs tested in cells, 2-DG, has been approved for emergency use against COVID-19 in some countries. Neogi, Elaldi et al. are now studying this further in animals with the hope of reaching clinical trials in the future.
- Published
- 2022
11. Screening of wild deer populations for exposure to SARS-CoV-2 in the United Kingdom, 2020-2021
- Author
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Maya Holding, Ashley David Otter, Stuart Dowall, Katsuhisa Takumi, Bethany Hicks, Tom Coleman, Georgia Hemingway, Matthew Royds, Stephen Findlay‐Wilson, Mollie Curran‐French, Richard Vipond, Hein Sprong, and Roger Hewson
- Subjects
COVID-19 Testing ,General Veterinary ,General Immunology and Microbiology ,SARS-CoV-2 ,Deer ,Spike Glycoprotein, Coronavirus ,Animals ,COVID-19 ,Humans ,Animals, Wild ,General Medicine ,Antibodies, Viral - Abstract
Following findings in Northern America of SARS-CoV-2 infections in white-tailed deer, there is concern of similar infections in European deer and their potential as reservoirs of SARS-CoV-2 including opportunities for the emergence of new variants. UK deer sera were collected in 2020-2021 from 6 species and a hybrid with 1748 tested using anti-spike and anti-nucleocapsid serology assays. No samples were positive on both assays nor by surrogate neutralization testing. There is no evidence that spill-over infections of SARS-CoV-2 occurred from the human population to UK deer or that SARS-CoV-2 has been circulating in UK deer (over the study period). Although it cannot be ruled out, study results indicate that spill-over infections followed by circulation of SARS-CoV-2 to the most common European deer species is small.
- Published
- 2022
12. Author response: Multi-omics insights into host-viral response and pathogenesis in Crimean-Congo hemorrhagic fever viruses for novel therapeutic target
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Nazif Elaldi, Ujjwal Neogi, Sofia Appelberg, Anoop Ambikan, Emma Kennedy, Stuart Dowall, Binnur K Bagci, Soham Gupta, Jimmy E Rodriguez, Sara Svensson-Akusjärvi, Vanessa Monteil, Akos Vegvari, Rui Benfeitas, Akhil Banerjea, Friedemann Weber, Roger Hewson, and Ali Mirazimi
- Published
- 2022
13. Tick-Borne Encephalitis Virus, United Kingdom
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Richard Vipond, Daniel P. Carter, Matthew Baylis, Mara S Rocchi, Steven T. Pullan, James S. Lewis, Roger Hewson, Jolyon M Medlock, Maya Holding, and Stuart D. Dowall
- Subjects
Male ,Epidemiology ,Tick-Borne Encephalitis Virus, United Kingdom ,tickborne infections ,Ixodes ricinus ,vector-borne infections ,lcsh:Medicine ,TBEV ,0302 clinical medicine ,flavivirus ,030212 general & internal medicine ,Phylogeny ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,tick-borne encephalitis ,louping ill virus ,Flavivirus ,Tick-borne encephalitis virus ,Infectious Diseases ,RNA, Viral ,Female ,meningitis/encephalitis ,Encephalitis ,Encephalitis, Tick-Borne ,Microbiology (medical) ,Ixodidae ,tick-borne encephalitis virus ,030231 tropical medicine ,Enzyme-Linked Immunosorbent Assay ,Tick ,Virus ,lcsh:Infectious and parasitic diseases ,Encephalitis Viruses, Tick-Borne ,ticks ,03 medical and health sciences ,Louping ill virus ,parasitic diseases ,medicine ,Animals ,Humans ,lcsh:RC109-216 ,viruses ,sentinel animals ,Sequence Analysis, RNA ,Research ,lcsh:R ,Tick-borne encephalitis ,Hemagglutination Inhibition Tests ,biology.organism_classification ,medicine.disease ,Virology ,United Kingdom ,zoonoses ,Sentinel Species ,deer ,immunological surveillance - Abstract
During February 2018–January 2019, we conducted large-scale surveillance for the presence and prevalence of tick-borne encephalitis virus (TBEV) and louping ill virus (LIV) in sentinel animals and ticks in the United Kingdom. Serum was collected from 1,309 deer culled across England and Scotland. Overall, 4% of samples were ELISA-positive for the TBEV serocomplex. A focus in the Thetford Forest area had the highest proportion (47.7%) of seropositive samples. Ticks collected from culled deer within seropositive regions were tested for viral RNA; 5 of 2,041 ticks tested positive by LIV/TBEV real-time reverse transcription PCR, all from within the Thetford Forest area. From 1 tick, we identified a full-length genomic sequence of TBEV. Thus, using deer as sentinels revealed a potential TBEV focus in the United Kingdom. This detection of TBEV genomic sequence in UK ticks has important public health implications, especially for undiagnosed encephalitis.
- Published
- 2020
14. Prevalence of Antibodies to Crimean-Congo Hemorrhagic Fever Virus in Ruminants, Nigeria, 2015
- Author
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A I Adebiyi, Daniel Oladimeji Oluwayelu, Tomoki Yoshikawa, Masayuki Saijo, Oyewale Tomori, Anitha Varghese, Park Eunsil, Shuetsu Fukushi, Roger Hewson, Shigeru Morikawa, Babak Afrough, and E.J. Neumann
- Subjects
Microbiology (medical) ,Crimean–Congo hemorrhagic fever ,Epidemiology ,030231 tropical medicine ,prevalence ,lcsh:Medicine ,Nigeria ,Human pathogen ,Prevalence of Antibodies to Crimean-Congo Hemorrhagic Fever Virus in Ruminants, Nigeria, 2015 ,Antibodies, Viral ,Virus ,lcsh:Infectious and parasitic diseases ,03 medical and health sciences ,0302 clinical medicine ,Seroepidemiologic Studies ,CCHF ,antibodies Crimean-Congo hemorrhagic fever virus ,Medicine ,antibodies ,Animals ,lcsh:RC109-216 ,viruses ,030212 general & internal medicine ,biology ,business.industry ,lcsh:R ,Dispatch ,Ruminants ,Hemorrhagic fever virus ,medicine.disease ,Virology ,Crimean-Congo hemorrhagic fever virus ,zoonoses ,Infectious Diseases ,CCHFV ,Hemorrhagic Fever Virus, Crimean-Congo ,biology.protein ,Crimean-Congo hemorrhagic fever ,Cattle ,Hemorrhagic Fever, Crimean ,Antibody ,business ,Crimean Congo hemorrhagic fever virus - Abstract
Crimean-Congo hemorrhagic fever virus (CCHFV) is a highly transmissible human pathogen. Infection is often misdiagnosed, in part because of poor availability of data in disease-endemic areas. We sampled 150 apparently healthy ruminants throughout Nigeria for virus seropositivity and detected virus-specific IgG in cattle (24%) and goats (2%), highlighting the need for further investigations.
- Published
- 2020
15. Cooperative Research and Infectious Disease Surveillance: A 2021 Epilogue
- Author
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Falgunee K. Parekh, John Hay, Kairat Tabynov, Roger Hewson, Jeanne M. Fair, Sandra Essbauer, and Kenneth B. Yeh
- Subjects
SARS-CoV-2 ,International Cooperation ,Public Health, Environmental and Occupational Health ,COVID-19 ,cooperative research ,infectious disease surveillance ,Communicable Diseases ,Perspective ,Humans ,Public Health ,scientific publication ,Public aspects of medicine ,RA1-1270 ,Pandemics ,global health security - Abstract
As the world looks forward to turning a corner in the face of the COVID-19 pandemic, it becomes increasingly evident that international research cooperation and dialogue is necessary to end this global catastrophe. Last year, we initiated a research topic: “Infectious Disease Surveillance: Cooperative Research in Response to Recent Outbreaks, Including COVID-19,” which aimed at featuring manuscripts focused on the essential link between surveillance and cooperative research for emerging and endemic diseases, and highlighting scientific partnerships in countries under-represented in the scientific literature. Here we recognize the body of work published from our manuscript call that resulted in over 50 published papers. This current analysis describes articles and authors from a variety of funded and unfunded international sources. The work exemplifies successful research and publications which are frequently cooperative, and may serve as a basis to model further global scientific engagements.
- Published
- 2022
16. Novel orthonairovirus in rodents and shrews, Gabon
- Author
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Takehiro Ozeki, Haruka Abe, Yuri Ushijima, Chiméne Nze-Nkogue, Etienne F Akomo-Okoue, Ghislain W.E Ella, Lilian B.M Koumba, Branly C.B.B Nzo, Rodrigue Mintsa-Nguema, Patrice Makouloutou-Nzassi, Boris K Makanga, Fred L.M Nguelet, Georgelin N Ondo, Marien J.V.M Mbadinga, Yui Igasaki, Sayaka Okada, Bertrand Lell, Laura C. Bonney, Roger Hewson, Yohei Kurosaki, and Jiro Yasuda
- Subjects
viruses ,parasitic diseases - Abstract
Small mammals harbor various zoonotic viruses and are natural reservoirs for emerging viruses. Here, we identified a novel orthonairovirus, which is genetically close to the virus suggested the association with human neural diseases. The virus was found in 24.6% of the small mammals captured in Gabon, Central Africa.
- Published
- 2022
17. Development of a Hamster Natural Transmission Model of SARS-CoV-2 Infection
- Author
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Graham J. Hatch, Simon Parks, Rachel Fell, Kathryn Gowan, Karen Gooch, Nathan Wiblin, Stuart Dowall, Robert J. Watson, Debbie Harris, Roger Hewson, Susan A. Fotheringham, Francisco J. Salguero, Yper Hall, Oliver Carnell, Victoria Graham, and Simon Mizen
- Subjects
Male ,Hamster ,Disease ,Biology ,medicine.disease_cause ,Microbiology ,Virus ,Article ,Pathogenesis ,Virology ,Cricetinae ,medicine ,Respiratory system ,Viral shedding ,Lung ,Coronavirus ,Mesocricetus ,Transmission (medicine) ,SARS-CoV-2 ,transmission ,COVID-19 ,Viral Load ,QR1-502 ,Virus Shedding ,animals ,Disease Models, Animal ,Infectious Diseases ,Female ,Nasal Cavity - Abstract
The global pandemic of coronavirus disease (COVID-19) caused by infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to an international thrust to study pathogenesis and evaluate interventions. Experimental infection of hamsters and the resulting respiratory disease is one of the preferred animal models since clinical signs of disease and virus shedding are similar to more severe cases of human COVID-19. The main route of challenge has been direct inoculation of the virus via the intranasal route. To resemble the natural infection, we designed a bespoke natural transmission cage system to assess whether recipient animals housed in physically separate adjacent cages could become infected from a challenged donor animal in a central cage, with equal airflow across the two side cages. To optimise viral shedding in the donor animals, a low and moderate challenge dose were compared after direct intranasal challenge, but similar viral shedding responses were observed and no discernible difference in kinetics. The results from our natural transmission set-up demonstrate that most recipient hamsters are infected within the system developed, with variation in the kinetics and levels of disease between individual animals. Common clinical outputs used for the assessment in directly-challenged hamsters, such as weight loss, are less obvious in hamsters who become infected from naturally acquiring the infection. The results demonstrate the utility of a natural transmission model for further work on assessing the differences between virus strains and evaluating interventions using a challenge system which more closely resembles human infection.
- Published
- 2021
18. Building Scientific Capability and Reducing Biological Threats: The Effect of Three Cooperative Bio-Research Programs in Kazakhstan
- Author
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Kenneth B. Yeh, Kairat Tabynov, Falgunee K. Parekh, Elina Maltseva, Yuriy Skiba, Zhanna Shapiyeva, Ablay Sansyzbai, Stefan Frey, Sandra Essbauer, Roger Hewson, Allen L. Richards, and John Hay
- Subjects
Knowledge management ,Cooperative research ,media_common.quotation_subject ,Mini Review ,Biosecurity ,vector-borne disease ,Global Health ,German ,Agency (sociology) ,Global health ,Quality (business) ,one health approach ,media_common ,global health security ,business.industry ,Public Health, Environmental and Occupational Health ,language.human_language ,United States ,Kazakhstan ,zoonoses ,Capability Maturity Model ,language ,Public Health ,Public aspects of medicine ,RA1-1270 ,business ,biosecurity - Abstract
Cooperative research programs aimed at reducing biological threats have increased scientific capabilities and capacities in Kazakhstan. The German Federal Foreign Office's German Biosecurity Programme, the United Kingdom's International Biological Security Programme and the United States Defense Threat Reduction Agency's Biological Threat Reduction Program provide funding for partner countries, like Kazakhstan. The mutual goals of the programs are to reduce biological threats and enhance global health security. Our investigation examined these cooperative research programs, summarizing major impacts they have made, as well as common successes and challenges. By mapping various projects across the three programs, research networks are highlighted which demonstrate best communication practices to share results and reinforce conclusions. Our team performed a survey to collect results from Kazakhstani partner scientists on their experiences that help gain insights into enhancing day-to-day approaches to conducting cooperative scientific research. This analysis will serve as a basis for a capability maturity model as used in industry, and in addition builds synergy for future collaborations that will be essential for quality and sustainment.
- Published
- 2021
19. Operationalizing Cooperative Research for Infectious Disease Surveillance: Lessons Learned and Ways Forward
- Author
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Kairat Tabynov, John Hay, Jeanne M. Fair, Sandra Essbauer, Kaissar Tabynov, Roger Hewson, Kenneth B. Yeh, and Falgunee K. Parekh
- Subjects
Biosecurity ,infectious disease surveillance ,Communicable Diseases ,Disease Outbreaks ,Central Asia ,Pandemic ,Humans ,Pandemics ,global health security ,Operationalization ,SARS-CoV-2 ,capacity building ,Public Health, Environmental and Occupational Health ,Capacity building ,COVID-19 ,cooperative research ,Identification (information) ,Risk analysis (engineering) ,Infectious disease (medical specialty) ,Preparedness ,Transparency (graphic) ,Perspective ,Business ,Public Health ,Public aspects of medicine ,RA1-1270 - Abstract
The current COVID-19 pandemic demonstrates the need for urgent and on-demand solutions to provide diagnostics, treatment and preventative measures for infectious disease outbreaks. Once solutions are developed, meeting capacities depends on the ability to mitigate technical, logistical and production issues. While it is difficult to predict the next outbreak, augmenting investments in preparedness, such as infectious disease surveillance, is far more effective than mustering last-minute response funds. Bringing research outputs into practice sooner rather than later is part of an agile approach to pivot and deliver solutions. Cooperative multi- country research programs, especially those funded by global biosecurity programs, develop capacity that can be applied to infectious disease surveillance and research that enhances detection, identification, and response to emerging and re-emerging pathogens with epidemic or pandemic potential. Moreover, these programs enhance trust building among partners, which is essential because setting expectation and commitment are required for successful research and training. Measuring research outputs, evaluating outcomes and justifying continual investments are essential but not straightforward. Lessons learned include those related to reducing biological threats and maturing capabilities for national laboratory diagnostics strategy and related health systems. Challenges, such as growing networks, promoting scientific transparency, data and material sharing, sustaining funds and developing research strategies remain to be fully resolved. Here, experiences from several programs highlight successful partnerships that provide ways forward to address the next outbreak.
- Published
- 2021
20. Detection of Rift Valley Fever Virus RNA in Formalin-Fixed Mosquitoes by In Situ Hybridization (RNAscope®)
- Author
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Nicholas Johnson, Anthony R. Fooks, Roger Hewson, Daniel L. Horton, Kirsty Emery, Laura Hunter, and Sarah Lumley
- Subjects
0301 basic medicine ,Rift Valley fever virus ,Rift Valley Fever ,Range (biology) ,030231 tropical medicine ,mosquito ,Mosquito Vectors ,In situ hybridization ,Biology ,Microbiology ,Virus ,03 medical and health sciences ,0302 clinical medicine ,Virology ,Culex pipiens ,parasitic diseases ,Animals ,In Situ Hybridization ,virus detection ,Transmission (medicine) ,Brief Report ,fungi ,RNA ,Outbreak ,biology.organism_classification ,Immunohistochemistry ,QR1-502 ,Culicidae ,030104 developmental biology ,Infectious Diseases - Abstract
Rift Valley fever virus (RVFV) causes a zoonotic mosquito-borne haemorrhagic disease that emerges to produce rapid large-scale outbreaks in livestock within sub-Saharan Africa. A range of mosquito species in Africa have been shown to transmit RVFV, and recent studies have assessed whether temperate mosquito species are also capable of transmission. In order to support vector competence studies, the ability to visualize virus localization in mosquito cells and tissue would enhance the understanding of the infection process within the mosquito body. Here, the application of in situ hybridization utilizing RNAscope® to detect RVFV infection within the mosquito species, Culex pipiens, derived from the United Kingdom was demonstrated. Extensive RVFV replication was detected in many tissues of the mosquito with the notable exception of the interior of ovarian follicles.
- Published
- 2021
21. Longitudinal blood cell transcriptomic profiling and in vitro temporal proteomics provides novel insights into metabolic reprogramming and host-immune responses against Crimean-Congo Hemorrhagic Fever Virus
- Author
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Friedemann Weber, Binnur Bagci, Soham Gupta, Vegvari A, Banerjea A, Emma Kennedy, Anoop T. Ambikan, Sofia Appelberg, Dowall S, Roger Hewson, Monteil, Akusjärvi Ss, Rodriguez J, Ali Mirazimi, Neogi U, and Nazif Elaldi
- Subjects
Transcriptome ,Blood cell ,Immune system ,medicine.anatomical_structure ,Host (biology) ,Metabolic reprogramming ,medicine ,Biology ,Proteomics ,Virology ,Crimean Congo hemorrhagic fever virus ,In vitro - Abstract
The pathogenesis and host-viral interactions of the Crimean–Congo hemorrhagic fever orthonairovirus (CCHFV) are convoluted and is not well evaluated. To understand the host immune responses against CCHFV, we have performed a global transcriptomic analysis of peripheral blood mononuclear cells from a longitudinal cohort of CCHF patients who survived the infection and temporal untargeted proteomics analysis of CCHFV infected Huh7 cells. Our results indicate that during the acute phase of CCHFV infection, the host's metabolic reprogramming towards central carbon metabolism including glycolysis and glutaminolysis occurs that favours the virus replication as blocking these pathways in vitro inhibits CCHFV cellular replication. Furthermore, CCHFV replication was inhibited by blocking Akt with MK-2206 suggesting a regulatory role of PI3K/Akt/mTOR pathways. We also show activation of key interferon stimulating genes during infection, suggesting a role for type I and II interferon-mediated antiviral mechanisms. Targeting immune-metabolic pathways could be attractive therapeutic intervention for CCHFV.
- Published
- 2021
22. A vaccine based on recombinant modified Vaccinia Ankara containing the nucleoprotein from Lassa virus protects against disease progression in a guinea pig model
- Author
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Eamonn Kennedy, Roger Hewson, Stuart D. Dowall, Francisco J. Salguero, Marilyn Aram, and Paul Yeates
- Subjects
Modified vaccinia Ankara ,viruses ,Guinea Pigs ,030231 tropical medicine ,Enzyme-Linked Immunosorbent Assay ,Vaccinia virus ,medicine.disease_cause ,complex mixtures ,Cell Line ,03 medical and health sciences ,0302 clinical medicine ,Immunity ,Cricetinae ,Vaccinia ,medicine ,Animals ,030212 general & internal medicine ,Lassa virus ,Lassa fever ,Vaccines, Synthetic ,General Veterinary ,General Immunology and Microbiology ,business.industry ,Immunogenicity ,ELISPOT ,Vaccination ,Public Health, Environmental and Occupational Health ,medicine.disease ,Virology ,Nucleoprotein ,Nucleoproteins ,Infectious Diseases ,Molecular Medicine ,Female ,business - Abstract
Lassa fever remains the most imported viral haemorrhagic fever in Europe and is responsible for 5000 deaths per year throughout Western Africa. There is no vaccine and treatment is often ineffective. We have developed a vaccine based on modified Vaccinia Ankara expressing the nucleoprotein from Lassa virus (MVALassaNP). This study investigated the immunogenicity (in mice) and efficacy (in guinea pigs) of the MVALassaNP vaccine as a prime/boost or single vaccination regime. ELISA and ELISpot assays confirmed humoral and T-cell immunity following both a prime and prime/boost vaccination, with the prime/boost regime producing a statistically increased response compared to a prime only vaccine (P
- Published
- 2019
23. Development, validation and clinical evaluation of a broad-range pan-filovirus RT-qPCR
- Author
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Moussa Moïse Diagne, Robert J. Watson, Amadou A. Sall, Ousmane Faye, Roger Hewson, Olli Vapalahti, Martin Faye, Oumar Faye, Anne J. Jääskeläinen, Markos Molsa, Tarja Sironen, Manfred Weidmann, Cheikh Tidiane Diagne, Medicum, Viral Zoonosis Research Unit, Department of Virology, University of Helsinki, Clinicum, HUSLAB, Veterinary Biosciences, Faculty of Veterinary Medicine, Veterinary Microbiology and Epidemiology, Olli Pekka Vapalahti / Principal Investigator, Helsinki One Health (HOH), and Emerging Infections Research Group
- Subjects
0301 basic medicine ,Tai Forest virus ,030106 microbiology ,Real-Time Polymerase Chain Reaction ,medicine.disease_cause ,Sensitivity and Specificity ,DISEASE ,law.invention ,West africa ,Sudan ,Viral Proteins ,Marburg ,03 medical and health sciences ,0302 clinical medicine ,Limit of Detection ,law ,Virology ,Filoviridae Infections ,medicine ,Animals ,Humans ,Marburg Virus Disease ,Bundibugyo ,030212 general & internal medicine ,1183 Plant biology, microbiology, virology ,Polymerase chain reaction ,Ebola virus ,Pan-Filo ,biology ,Outbreak ,KIT ,Hemorrhagic Fever, Ebola ,Ebolavirus ,Filoviridae ,Marburgvirus ,biology.organism_classification ,3. Good health ,EBOLA-VIRUS ,Freeze Drying ,Infectious Diseases ,BATS ,Ebola ,INACTIVATION ,3111 Biomedicine ,Clinical evaluation ,Viral load - Abstract
Background During the five decades since their discovery, filoviruses of four species have caused human hemorrhagic fever outbreaks: Marburg (MARV) marburgvirus, and Zaire (EBOV), Sudan (SUDV) and Bundybugyo (BDBV) ebolaviruses. The largest, devastating EBOV epidemic in West Africa in 2014-16, has been followed by outbreaks of MARV in Uganda, 2017, and EBOV in Democratic Republic of Congo, 2018, emphasizing the need to develop preparedness to diagnose all filoviruses. Objectives The aim of this study was to optimize a new filovirus RT-qPCR to detect all filoviruses, define its limits of detection (LOD) and perform a field evaluation with outbreak samples. Study design A pan-filovirus RT-qPCR targeting the L gene was developed and evaluated within the EbolaMoDRAD (Ebola virus: modern approaches for developing bedside rapid diagnostics) project. Specificity and sensitivity were determined and the effect of inactivation and PCR reagents (liquid and lyophilized format) were tested. Results The LODs for the lyophilized pan-filovirus L-RT-qPCR assay were 9.4 copies per PCR reaction for EBOV, 9.9 for MARV, 1151 for SUDV, 65 for BDBV and 289 for Tai Forest virus. The test was set at the Pasteur Institute, Dakar, Senegal, and 83 Ebola patient samples, with viral load ranging from 5 to 5 million copies of EBOV per reaction, were screened. The results for the patient samples were in 100% concordance with the reference EBOV-specific assay. Discussion Overall, the assay showed good sensitivity and specificity, covered all filoviruses known to be human pathogens, performed well both in lyophilized and liquid-phase formats and with EBOV outbreak clinical samples.
- Published
- 2019
24. Cellular cholesterol abundance regulates potassium accumulation within endosomes and is an important determinant in bunyavirus entry
- Author
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Jack Fuller, Juan Fontana, Jamel Mankouri, Frank W. Charlton, Roger Hewson, Samantha Hover, and John N. Barr
- Subjects
0301 basic medicine ,Orthobunyavirus ,Endosome ,Cell ,Endocytic cycle ,Endosomes ,Biology ,medicine.disease_cause ,Biochemistry ,Virus ,chemistry.chemical_compound ,03 medical and health sciences ,Bunyamwera virus ,Viral entry ,Cell Line, Tumor ,medicine ,Humans ,General Materials Science ,Molecular Biology ,Ion Transport ,030102 biochemistry & molecular biology ,Cholesterol ,Virion ,RNA ,Cell Biology ,Virus Internalization ,Endocytosis ,Cell biology ,Cytosol ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Potassium ,Homeostasis - Abstract
The Bunyavirales order of segmented negative sense RNA viruses includes over 500 isolates that infect insects, animals, and plants, and are often associated with severe and fatal disease in humans. To multiply and cause disease, bunyaviruses must transport their genomes from outside the cell into the cytosol, achieved by transit through the endocytic network. We have previously shown that the model bunyaviruses Bunyamwera virus (BUNV) and Hazara virus (HAZV) exploit the changing potassium concentration ([K+]) of maturing endosomes to release their genomes at the appropriate endosomal location. K+ was identified as a biochemical cue to activate the viral fusion machinery, promoting fusion between viral and cellular membranes, consequently permitting genome release. In this study, we further define the biochemical prerequisites for BUNV and HAZV entry and their K+ dependence. We report four major findings: (1) BUNV and HAZV require cellular cholesterol during virus infection; (2) cholesterol is required during BUNV endosomal escape; (3) cholesterol depletion from host cells impairs their ability to accumulate K+ in maturing endosomes, revealing new insights into endosomal K+ homeostasis; (4) ‘priming’ BUNV virions with K+ prior to infection alleviates BUNV cholesterol requirement, revealing the mechanism of cholesterol dependence. Taken together, we provide a new model in which cholesterol abundance influences K+ endosomal homeostasis and consequently the efficiency of bunyavirus infection. The ability to inhibit bunyaviruses with existing cholesterol lowering drugs offers new options for future anti-bunyavirus interventions for pathogenic family members.
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- 2019
25. Emerging viruses and current strategies for vaccine intervention
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Roger Hewson, Stuart D. Dowall, and Babak Afrough
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0301 basic medicine ,medicine.medical_specialty ,Immunology ,Review Article ,Antibodies, Viral ,Virus ,Viral vector ,03 medical and health sciences ,0302 clinical medicine ,Intervention (counseling) ,Global health ,medicine ,molecular biology ,Animals ,Humans ,Immunology and Allergy ,Intensive care medicine ,Review Articles ,Transmission (medicine) ,Vaccination ,Viral Vaccines ,Vaccines for Emerging Pathogens: from Research to the Clinic. Part 1. Series Editor: E Diane Williamson ,030104 developmental biology ,Virus Diseases ,Viruses ,Disease prevention ,Viral disease ,viral ,030215 immunology - Abstract
Summary During the past decade several notable viruses have suddenly emerged from obscurity or anonymity to become serious global health threats, provoking concern regarding their sustained epidemic transmission in immunologically naive human populations. With each new threat comes the call for rapid vaccine development. Indeed, vaccines are considered a critical component of disease prevention for emerging viral infections because, in many cases, other medical options are limited or non-existent, or that infections result in such a rapid clinical deterioration that the effectiveness of therapeutics is limited. While classic approaches to vaccine development are still amenable to emerging viruses, the application of molecular techniques in virology has profoundly influenced our understanding of virus biology, and vaccination methods based on replicating, attenuated and non-replicating virus vector approaches have become useful vaccine platforms. Together with a growing understanding of viral disease emergence, a range of vaccine strategies and international commitment to underpin development, vaccine intervention for new and emerging viruses may become a possibility.
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- 2019
26. Use and reliability of multiplex bead-based assays (Luminex) at Containment Level 4
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Victoria A. Graham, Tom Fletcher, Roger Hewson, and Stuart D. Dowall
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Quality Control ,Biosafety level 4 ,Validation study ,Tissue Fixation ,Class iii ,Communicable Diseases ,Microbiology ,General Biochemistry, Genetics and Molecular Biology ,Microsphere ,Fixatives ,03 medical and health sciences ,Sample volume ,Formaldehyde ,Humans ,Multiplex ,Molecular Biology ,Reliability (statistics) ,030304 developmental biology ,0303 health sciences ,Containment (computer programming) ,030302 biochemistry & molecular biology ,Reproducibility of Results ,Clinical Laboratory Services ,Containment of Biohazards ,Microspheres ,High-Throughput Screening Assays ,Biochemical engineering ,Laboratories - Abstract
In the UK, research on hazard group 4 (HG4) pathogens requires specialised Containment Level 4 (CL4) facilities. These differ from Biosafety Level 4 (BSL4) conditions in that work is conducted in class III microbiological safety cabinets for primary containment instead of using positive pressure suits. This presents unique challenges associated with the physical restrictions of working in a limited space, and prohibits the use of many techniques and specialist equipment. In consequence, detailed studies on the biology of HG4 pathogens and in particular their immunological relationships with the host are understudied in the UK; for example, the majority of immunological assays with which the immune system is interrogated require specialist equipment that is unsuitable for CL4. Multiplexing to simultaneously measure multiple analytes is increasingly being used in immunological studies. This assay is attractive for CL4 work because it reduces the time spent in the laboratory whilst maximising the use of valuable sample volume. The Luminex microsphere approach allows for the determination of many cytokines and chemokines, however, the detection system uses fixed aligned lasers and integrated computer systems which are unsuitable for use at CL4. Therefore, we have developed an approach in which the Luminex assay is conducted within the CL4 laboratory and a formalin-fixation stage is introduced to allow for analysis to be undertaken outside of containment. Quality control preparations allow the assay characteristics to be monitored and analysis of assay performance to be evaluated. Our data demonstrate that Luminex is an applicable tool for use at CL4 and that assays can be run reliably to generate reproducible standardised data across different plates and individual experiments.
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- 2019
27. Laboratory management of Crimean-Congo haemorrhagic fever virus infections: perspectives from two European networks
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Chantal Reusken, Hervé Zeller, Gulay Korukluoglu, Anna Papa, Cinthia Menel Lemos, Roger Hewson, Barbara Bartolini, Ali Mirazimi, Giuseppe Ippolito, Cesare Ernesto Maria Gruber, Antonino Di Caro, Roland Grunow, María Paz Sánchez-Seco, Sylvia Bino, Marion Koopmans, Aisha V. Sauer, Tatjana Avšič, Carla Nisii, Iva Christova, Maria Rosaria Capobianchi, Virology, Unión Europea, European Centre for Disease Prevention and Control, and Unión Europea. Comisión Europea
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0301 basic medicine ,Laboratory Proficiency Testing ,Epidemiology ,Review ,Disease ,emerging diseases ,Communicable Diseases, Emerging ,Disease Outbreaks ,Biosafety ,Ticks ,Infection control ,media_common ,Emerging diseases ,Crimean-Congo haemorrhagic fever virus ,3. Good health ,Preparedness ,Hemorrhagic Fever Virus, Crimean-Congo ,Emerging infectious disease ,medicine.medical_specialty ,Ixodidae ,030106 microbiology ,Enzyme-Linked Immunosorbent Assay ,03 medical and health sciences ,Virology ,CCHF ,medicine ,Animals ,Humans ,laboratory preparedness ,media_common.cataloged_instance ,ddc:610 ,European union ,Intensive care medicine ,laboratory response ,Clinical Laboratory Techniques ,Sequence Analysis, RNA ,business.industry ,Public health ,Public Health, Environmental and Occupational Health ,Outbreak ,European network ,030104 developmental biology ,CCHFV ,Immunoglobulin G ,Laboratory preparedness ,DNA, Viral ,Hemorrhagic Fever, Crimean ,Laboratories ,610 Medizin und Gesundheit ,business ,Laboratory response - Abstract
Background Crimean-Congo haemorrhagic fever virus (CCHFV) is considered an emerging infectious disease threat in the European Union. Since 2000, the incidence and geographic range of confirmed CCHF cases have markedly increased, following changes in the distribution of its main vector, Hyalomma ticks. Aims To review scientific literature and collect experts’ opinion to analyse relevant aspects of the laboratory management of human CCHF cases and any exposed contacts, as well as identify areas for advancement of international collaborative preparedness and laboratory response plans. Methods We conducted a literature review on CCHF molecular diagnostics through an online search. Further, we obtained expert opinions on the key laboratory aspects of CCHF diagnosis. Consulted experts were members of two European projects, EMERGE (Efficient response to highly dangerous and emerging pathogens at EU level) and EVD-LabNet (Emerging Viral Diseases-Expert Laboratory Network). Results Consensus was reached on relevant and controversial aspects of CCHF disease with implications for laboratory management of human CCHF cases, including biosafety, diagnostic algorithm and advice to improve lab capabilities. Knowledge on the diffusion of CCHF can be obtained by promoting syndromic approach to infectious diseases diagnosis and by including CCHFV infection in the diagnostic algorithm of severe fevers of unknown origin. Conclusion No effective vaccine and/or therapeutics are available at present so outbreak response relies on rapid identification and appropriate infection control measures. Frontline hospitals and reference laboratories have a crucial role in the response to a CCHF outbreak, which should integrate laboratory, clinical and public health responses.
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- 2019
28. Exportation of Monkeypox virus from the African continent
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Eli Schwartz, Colin S Brown, Richard Vipond, Mary G. Reynolds, Matthew R. Mauldin, Jeffrey B. Doty, Dhamari Naidoo, Chikwe Ihekweazu, Olusola Aruna, Ofir Israeli, Hui Zhao, Noam Erez, Andrea M. McCollum, Nir Paran, Kuiama Lewandowski, Tze Minn Mak, Lin Cui, Ohad Shifman, Adi Beth-Din, Babak Afrough, Anna Mandra, Inbar Cohen-Gihon, Adesola Yinka-Ogunleye, Jinxin Gao, Raymond T. P. Lin, Tim Brooks, Melamed Sharon, Erin R. Whitehouse, Jake Dunning, Meera Chand, Afolabi Akinpelu, Emma Aarons, Roger Hewson, Yi Kai Ng, Yoshinori J. Nakazawa, Victoria A. Olson, Anat Zvi, Victoria A. Graham, Yu Li, and Whitni Davidson
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0301 basic medicine ,Delta ,030231 tropical medicine ,Nigeria ,Context (language use) ,Disease cluster ,Disease Outbreaks ,law.invention ,03 medical and health sciences ,Monkeypox ,0302 clinical medicine ,law ,Genetic variation ,medicine ,Humans ,Immunology and Allergy ,Monkeypox virus ,Socioeconomics ,biology ,Outbreak ,biology.organism_classification ,medicine.disease ,United Kingdom ,030104 developmental biology ,Infectious Diseases ,Geography ,Transmission (mechanics) - Abstract
Background The largest West African monkeypox outbreak began September 2017, in Nigeria. Four individuals traveling from Nigeria to the United Kingdom (n = 2), Israel (n = 1), and Singapore (n = 1) became the first human monkeypox cases exported from Africa, and a related nosocomial transmission event in the United Kingdom became the first confirmed human-to-human monkeypox transmission event outside of Africa. Methods Epidemiological and molecular data for exported and Nigerian cases were analyzed jointly to better understand the exportations in the temporal and geographic context of the outbreak. Results Isolates from all travelers and a Bayelsa case shared a most recent common ancestor and traveled to Bayelsa, Delta, or Rivers states. Genetic variation for this cluster was lower than would be expected from a random sampling of genomes from this outbreak, but data did not support direct links between travelers. Conclusions Monophyly of exportation cases and the Bayelsa sample, along with the intermediate levels of genetic variation, suggest a small pool of related isolates is the likely source for the exported infections. This may be the result of the level of genetic variation present in monkeypox isolates circulating within the contiguous region of Bayelsa, Delta, and Rivers states, or another more restricted, yet unidentified source pool.
- Published
- 2021
29. Vaccines for Emerging Viruses—A Comprehensive Update
- Author
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Roger Hewson
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Vaccination ,medicine.medical_specialty ,business.industry ,Transmission (medicine) ,Pandemic ,medicine ,Viral disease ,Vector (molecular biology) ,Human Virus ,Intensive care medicine ,business ,Virus ,Viral vector - Abstract
Over the past decade several notable viruses have suddenly emerged from obscurity to become serious public health problems and global threats, provoking concern about sustained epidemic and pandemic transmission in immunologically naive human populations. With each newly-emerged virus hazard comes the call for rapid vaccine development. Vaccines are an important component of disease prevention and control for emerging viral infections since in many cases other medical options are limited or non-existent and vaccines are also highly cost effective. Some infections for example may result in such a rapid clinical deterioration that the effectiveness of therapeutics is limited. Other new human virus infections maybe symptomless or cryptic and by the time a diagnosis is possible, a therapeutic maybe of limited use. While many classic approaches to vaccine development are amenable to emerging viruses, the application of molecular techniques in virology has profoundly influenced our understanding of virus biology and virus-host interactions, and so facilitated the development of new vaccine strategies and vaccine vector platforms. Vaccination approaches based on replicating, attenuated and non-replicating virus vector schemes have become useful vaccine tools. If our growing understanding of viral disease emergence and increasing range of vaccine strategies are coupled with an international commitment to underpin vaccine development, vaccine interventions for new and emerging viruses become a possibility.
- Published
- 2021
30. Correction to: 2021 Taxonomic update of phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales
- Author
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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
- Subjects
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
31. Development of a multiplex microsphere immunoassay for the detection of antibodies against highly pathogenic viruses in human and animal serum samples
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Peter T. Witkowski, John N. Barr, Angelika Lander, Emmanuel Couacy-Hymann, Petra Kreher, Emma K. Punch, Andreas Kurth, Brigitte G. Dorner, Roger Hewson, Andrea Marzi, Katharina Ahrens, Daniel Stern, Nicole Kromarek, Rebecca Surtees, Sabrina Weiss, and McElroy, Anita K
- Subjects
0301 basic medicine ,RNA viruses ,Serum Proteins ,Physiology ,viruses ,RC955-962 ,medicine.disease_cause ,Antibodies, Viral ,Pathology and Laboratory Medicine ,Biochemistry ,Serology ,0302 clinical medicine ,Arctic medicine. Tropical medicine ,Chiroptera ,Immune Physiology ,Bunyaviruses ,Medicine and Health Sciences ,Multiplex ,Enzyme-Linked Immunoassays ,Immunoassay ,Immune System Proteins ,biology ,medicine.diagnostic_test ,Nucleocapsid Proteins ,Microspheres ,Infectious Diseases ,Virus Diseases ,Medical Microbiology ,Filoviruses ,Viral Pathogens ,Viruses ,Blood Banks ,Public aspects of medicine ,RA1-1270 ,Antibody ,Pathogens ,Ebola Virus ,Research Article ,Primates ,030231 tropical medicine ,Immunology ,Research and Analysis Methods ,Microbiology ,Virus ,Antibodies ,03 medical and health sciences ,Antigen ,medicine ,Animals ,Humans ,Immunoassays ,Microbial Pathogens ,Hantavirus ,Ebola virus ,Biology and life sciences ,Hemorrhagic Fever Viruses ,Public Health, Environmental and Occupational Health ,Organisms ,Proteins ,Rift Valley fever virus ,Virology ,Health Care ,030104 developmental biology ,Health Care Facilities ,biology.protein ,Immunologic Techniques - Abstract
Surveillance of highly pathogenic viruses circulating in both human and animal populations is crucial to unveil endemic infections and potential zoonotic reservoirs. Monitoring the burden of disease by serological assay could be used as an early warning system for imminent outbreaks as an increased seroprevalance often precedes larger outbreaks. However, the multitude of highly pathogenic viruses necessitates the need to identify specific antibodies against several targets from both humans as well as from potential reservoir animals such as bats. In order to address this, we have developed a broadly reactive multiplex microsphere immunoassay (MMIA) for the detection of antibodies against several highly pathogenic viruses from both humans and animals. To this aim, nucleoproteins (NP) of Ebola virus (EBOV), Marburg virus (MARV) and nucleocapsid proteins (NP) of Crimean-Congo haemorrhagic fever virus, Rift Valley fever virus and Dobrava-Belgrade hantavirus were employed in a 5-plex assay for IgG detection. After optimisation, specific binding to each respective NP was shown by testing sera from humans and non-human primates with known infection status. The usefulness of our assay for serosurveillance was shown by determining the immune response against the NP antigens in a panel of 129 human serum samples collected in Guinea between 2011 and 2012 in comparison to a panel of 88 sera from the German blood bank. We found good agreement between our MMIA and commercial or in-house reference methods by ELISA or IIFT with statistically significant higher binding to both EBOV NP and MARV NP coupled microspheres in the Guinea panel. Finally, the MMIA was successfully adapted to detect antibodies from bats that had been inoculated with EBOV- and MARV- virus-like particles, highlighting the versatility of this technique and potentially enabling the monitoring of wildlife as well as human populations with this assay. We were thus able to develop and validate a sensitive and broadly reactive high-throughput serological assay which could be used as a screening tool to detect antibodies against several highly pathogenic viruses., Author summary Zoonotic pathogens, which are transmitted from their animal, arthropod or insect host to humans, have been responsible for some of the most devastating disease outbreaks in human history, including the largest Ebola virus disease outbreak in West Africa in 2014–2016, which resulted in over 28,000 infected persons and caused 11,310 deaths. Changes in land use practices, the climate and overall globalization concurrently brings human populations into closer contact with animals, arthropods, insects and the zoonotic pathogens they host, whilst increasing the possibility for local outbreaks to expand and spread internationally. Here we developed a multiplex serological assay that can be used to simultaneously detect IgG antibodies to 5 highly pathogenic zoonotic viruses, Ebola -, Marburg -, Crimean Congo haemorrhagic fever—, Dobrava-Belgrade- and Rift Valley fever virus. Our assay was designed to be able to detect antibodies to multiple species of viruses within each family, and was adapted to detect animal (specifically bat) as well as human antibodies. This assay could be used as a serological surveillance tool to monitor evidence of infection with several highly pathogenic viruses in human and wildlife populations, which is important for risk assessment and prevention of zoonotic human infectious disease outbreaks.
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- 2020
32. Passive immunisation of convalescent human anti-Zika plasma protects against challenge with New World Zika virus in cynomolgus macaques
- Author
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Mark Page, Jo Hall, Giada Mattiuzzo, Adrian Jenkins, Claire Ham, Neil Berry, Elaine Giles, Neil Almond, Yemisi Adedeji, Roger Hewson, Debbie Ferguson, and Sarah L. Kempster
- Subjects
0301 basic medicine ,lcsh:Immunologic diseases. Allergy ,Convalescent plasma ,030231 tropical medicine ,Immunology ,Diseases ,Microbiology ,lcsh:RC254-282 ,Article ,Virus ,Zika virus ,03 medical and health sciences ,0302 clinical medicine ,Immunity ,Medicine ,Pharmacology (medical) ,Pharmacology ,biology ,business.industry ,biology.organism_classification ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Virology ,Vaccination ,030104 developmental biology ,Infectious Diseases ,Passive immunisation ,South american ,biology.protein ,Antibody ,business ,lcsh:RC581-607 - Abstract
Zika virus (ZIKV) causes neurological complications in susceptible individuals, highlighted in the recent South American epidemic. Natural ZIKV infection elicits host responses capable of preventing subsequent re-infection, raising expectations for effective vaccination. Defining protective immune correlates will inform viral intervention strategies, particularly vaccine development. Non-human primate (NHP) species are susceptible to ZIKV and represent models for vaccine development. The protective efficacy of a human anti-ZIKV convalescent plasma pool (16/320-14) developed as a candidate reference material for a WHO International Standard was evaluated in macaques. Convalescent plasma administered to four cynomolgus macaques (Macaca fascicularis) intra-peritoneally 24 hrs prior to sub-cutaneous challenge with 103 pfu ZIKVPRVABC59 protected against detectable infection, with absence of detectable ZIKV RNA in blood and lymphoid tissues. Passively immunised anti-ZIKV immunoglobulin administered prior to time of challenge remained present only at very low levels 42 days post-challenge. Absence of de novo antibody responses in passively immunised macaques indicate sterilising immunity compared with naïve challenge controls that exhibited active ZIKV-specific IgM and IgG responses post-challenge. Demonstration that the presence of convalescent anti-ZIKV at levels of 400 IU/mL neutralising antibody protects against virus challenge provides a scientific framework for development of anti-ZIKV vaccines and facilitates regulatory approval.
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- 2020
33. Pseudotyping of VSV with Ebola virus glycoprotein is superior to HIV-1 for the assessment of neutralising antibodies
- Author
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Edward Wright, Fara Raymond Koundouno, Georgios Pollakis, Kimberley Steeds, Mandy Kader Kondé, Gillian S. Slack, Thomas Strecker, Miles W. Carroll, Sarah Katharina Fehling, Yper Hall, Joseph Akoi Bore, Julian A. Hiscox, Roger Hewson, and Stephanie Longet
- Subjects
viruses ,Immunology ,lcsh:Medicine ,Diseases ,medicine.disease_cause ,Article ,Virus ,Neutralization ,Viral Envelope Proteins ,Neutralization Tests ,Viral entry ,Virology ,medicine ,Humans ,lcsh:Science ,Multidisciplinary ,Ebola virus ,biology ,lcsh:R ,RNA virus ,Vesiculovirus ,Ebolavirus ,biology.organism_classification ,Antibodies, Neutralizing ,Viral Tropism ,Vesicular stomatitis virus ,HIV-1 ,Pseudotyping ,biology.protein ,lcsh:Q ,Antibody - Abstract
Ebola virus (EBOV) is an enveloped, single-stranded RNA virus that can cause Ebola virus disease (EVD). It is thought that EVD survivors are protected against subsequent infection with EBOV and that neutralising antibodies to the viral surface glycoprotein (GP) are potential correlates of protection. Serological studies are vital to assess neutralising antibodies targeted to EBOV GP; however, handling of EBOV is limited to containment level 4 laboratories. Pseudotyped viruses can be used as alternatives to live viruses, which require high levels of bio-containment, in serological and viral entry assays. However, neutralisation capacity can differ among pseudotyped virus platforms. We evaluated the suitability of EBOV GP pseudotyped human immunodeficiency virus type 1 (HIV-1) and vesicular stomatitis virus (VSV) to measure the neutralising ability of plasma from EVD survivors, when compared to results from a live EBOV neutralisation assay. The sensitivity, specificity and correlation with live EBOV neutralisation were greater for the VSV-based pseudotyped virus system, which is particularly important when evaluating EBOV vaccine responses and immuno-therapeutics. Therefore, the EBOV GP pseudotyped VSV neutralisation assay reported here could be used to provide a better understanding of the putative correlates of protection against EBOV.
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- 2020
34. Mutagenic Analysis of Hazara Nairovirus Nontranslated Regions during Single- and Multistep Growth Identifies both Attenuating and Functionally Critical Sequences for Virus Replication
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Beatriz Álvarez-Rodríguez, John N. Barr, Roger Hewson, Jamel Mankouri, Daniele F Mega, and Jack Fuller
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RNA, Untranslated ,Base pair ,Immunology ,Virus Replication ,Microbiology ,Virus ,03 medical and health sciences ,Transcription (biology) ,Virology ,Animals ,Humans ,Base Pairing ,Gene ,030304 developmental biology ,Genetics ,0303 health sciences ,Messenger RNA ,Nairovirus ,Microbial Viability ,Base Sequence ,biology ,030306 microbiology ,RNA ,Nucleocapsid Proteins ,biology.organism_classification ,Genome Replication and Regulation of Viral Gene Expression ,3. Good health ,Viral replication ,Mutagenesis ,Insect Science ,Hemorrhagic Fever Virus, Crimean-Congo ,RNA, Viral - Abstract
Hazara nairovirus (HAZV) is a member of the family Nairoviridae in the order Bunyavirales and closely related to Crimean-Congo hemorrhagic fever virus, which is responsible for severe and fatal human disease. The HAZV genome comprises three segments of negative-sense RNA, named S, M, and L, with nontranslated regions (NTRs) flanking a single open reading frame. NTR sequences regulate RNA synthesis and, by analogy with other segmented negative-sense RNA viruses, may direct activities such as virus assembly and innate immune modulation. The terminal-proximal nucleotides of 3′ and 5′ NTRs exhibit extensive terminal complementarity; the first 11 nucleotides are strictly conserved and form promoter element 1 (PE1), with adjacent segment-specific nucleotides forming PE2. To explore the functionality of NTR nucleotides within the context of the nairovirus multiplication cycle, we designed infectious HAZV mutants bearing successive deletions throughout both S segment NTRs. Fitness of rescued viruses was assessed in single-step and multistep growth, which revealed that the 3′ NTR was highly tolerant to change, whereas several deletions of centrally located nucleotides in the 5′ NTR led to significantly reduced growth, indicative of functional disruption. Deletions that encroached upon PE1 and PE2 ablated virus growth and identified additional adjacent nucleotides critical for viability. Mutational analysis of PE2 suggest that its signaling ability relies solely on interterminal base pairing and is an independent cis-acting signaling module. This study represents the first mutagenic analysis of nairoviral NTRs in the context of the infectious cycle, and the mechanistic implications of our findings for nairovirus RNA synthesis are discussed. IMPORTANCE Nairoviruses are a group of RNA viruses that include many serious pathogens of humans and animals, including one of the most serious human pathogens in existence, Crimean-Congo hemorrhagic fever virus. The ability of nairoviruses to multiply and cause disease is controlled in major part by nucleotides that flank the 3′ and 5′ ends of nairoviral genes, called nontranslated regions (NTRs). NTR nucleotides interact with other virus components to perform critical steps of the virus multiplication cycle, such as mRNA transcription and RNA replication, with other roles being likely. To better understand how NTRs work, we performed the first comprehensive investigation of the importance of NTR nucleotides in the context of the entire nairovirus replication cycle. We identified both dispensable and critical NTR nucleotides, as well as highlighting the importance of 3′ and 5′ NTR interactions in virus growth, thus providing the first functional map of the nairovirus NTRs.
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- 2020
35. UK vaccines network: Mapping priority pathogens of epidemic potential and vaccine pipeline developments
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Andrew J. H. Simpson, Mark P. Stevens, Gary Entrican, Christopher J. M. Whitty, Roger Hewson, Anthony R. Fooks, Joann L. Prior, Karl Simpson, Anna M. Kinsey, Margaret J Hosie, Rob Noad, Sarah C. Gilbert, and Miles W. Carroll
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Economic growth ,Biomedical Research ,Manufactured material ,MERS, Middle East Respiratory Syndrome ,CCHF, Crimean-Congo Haemorrhagic Fever ,Communicable Diseases, Emerging ,West africa ,0302 clinical medicine ,SARS, Severe Acute Respiratory Syndrome ,Priority ,NIAID, US National Institute of Allergy and Infectious Diseases ,030212 general & internal medicine ,Vaccines ,UKVN ,Africa, Western ,Infectious Diseases ,Molecular Medicine ,WHO, World Health Organisation ,CEPI, Coalition for Epidemic Preparedness Innovations ,Priority list ,030231 tropical medicine ,MVA, Modified vaccinia virus Ankara ,Epidemic ,World Health Organization ,Communicable Diseases ,Article ,World health ,Prime minister ,03 medical and health sciences ,Humans ,Ebola Vaccines ,Epidemics ,General Veterinary ,General Immunology and Microbiology ,Pathogen ,Public Health, Environmental and Occupational Health ,Network mapping ,Outbreak ,Congresses as Topic ,Hemorrhagic Fever, Ebola ,CHIKV, Chikungunya virus ,NCBI, National Centre for Biotechnology Information ,United Kingdom ,United States ,Clinical trial ,National Institutes of Health (U.S.) ,VSV, Vesicular Stomatitis Virus ,Communicable Disease Control ,UKVN, UK Vaccine Research and Development Network ,Business ,Vaccine - Abstract
During the 2013-2016 Ebola outbreak in West Africa an expert panel was established on the instructions of the UK Prime Minister to identify priority pathogens for outbreak diseases that had the potential to cause future epidemics. A total of 13 priority pathogens were identified, which led to the prioritisation of spending in emerging diseases vaccine research and development from the UK. This meeting report summarises the process used to develop the UK pathogen priority list, compares it to lists generated by other organisations (World Health Organisation, National Institutes of Allergy and Infectious Diseases) and summarises clinical progress towards the development of vaccines against priority diseases. There is clear technical progress towards the development of vaccines. However, the availability of these vaccines will be dependent on sustained funding for clinical trials and the preparation of clinically acceptable manufactured material during inter-epidemic periods.
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- 2020
36. Hazara Nairovirus Requires COPI Components in both Arf1-Dependent and Arf1-Independent Stages of Its Replication Cycle
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Beatriz Álvarez-Rodríguez, John N. Barr, Jamel Mankouri, Roger Hewson, Jack Fuller, Eleanor J. A. A. Todd, and Dutch, Rebecca Ellis
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Gene Expression Regulation, Viral ,Immunology ,Golgi Apparatus ,Biology ,Endoplasmic Reticulum ,Virus Replication ,Microbiology ,Coat Protein Complex I ,03 medical and health sciences ,symbols.namesake ,chemistry.chemical_compound ,Viral entry ,cell biology ,Animals ,Spotlight ,RNA, Small Interfering ,030304 developmental biology ,COPI ,0303 health sciences ,Gene knockdown ,Nairovirus ,Brefeldin A ,030306 microbiology ,Endoplasmic reticulum ,Golgi apparatus ,biology.organism_classification ,host factors ,3. Good health ,Cell biology ,Virus-Cell Interactions ,virology ,Protein Transport ,chemistry ,Coatomer ,Insect Science ,Gene Knockdown Techniques ,Host-Pathogen Interactions ,symbols ,ADP-Ribosylation Factor 1 - Abstract
Nairoviruses are tick-borne enveloped RNA viruses that include several pathogens responsible for fatal disease in humans and animals. Here, we analyzed host genes involved in trafficking networks to examine their involvement in nairovirus replication. We revealed important roles for genes that express multiple components of the COPI complex, which regulates transport of Golgi apparatus-resident cargos. COPI components influenced at least two stages of the nairovirus replication cycle: an early stage prior to and including gene expression and also a later stage during assembly of infectious virus, with COPI knockdown reducing titers by approximately 1,000-fold. Importantly, while the late stage was Arf1 dependent, as expected for canonical COPI vesicle formation, the early stage was found to be Arf1 independent, suggestive of a previously unreported function of COPI unrelated to vesicle formation. Collectively, these data improve our understanding of nairovirus host-pathogen interactions and suggest a new Arf1-independent role for components of the COPI coatomer complex., Hazara nairovirus (HAZV) is an enveloped trisegmented negative-strand RNA virus classified within the Nairoviridae family of the Bunyavirales order and a member of the same subtype as Crimean-Congo hemorrhagic fever virus, responsible for fatal human disease. Nairoviral subversion of cellular trafficking pathways to permit viral entry, gene expression, assembly, and egress is poorly understood. Here, we generated a recombinant HAZV expressing enhanced green fluorescent protein and used live-cell fluorescent imaging to screen an siRNA library targeting genes involved in cellular trafficking networks, the first such screen for a nairovirus. The screen revealed prominent roles for subunits of the coat protein 1 (COPI)-vesicle coatomer, which regulates retrograde trafficking of cargo between the Golgi apparatus and the endoplasmic reticulum, as well as intra-Golgi transport. We show the requirement of COPI-coatomer subunits impacted at least two stages of the HAZV replication cycle: an early stage prior to and including gene expression and also a later stage during assembly and egress of infectious virus, with COPI-knockdown reducing titers by approximately 1,000-fold. Treatment of HAZV-infected cells with brefeldin A (BFA), an inhibitor of Arf1 activation required for COPI coatomer formation, revealed that this late COPI-dependent stage was Arf1 dependent, consistent with the established role of Arf1 in COPI vesicle formation. In contrast, the early COPI-dependent stage was Arf1 independent, with neither BFA treatment nor siRNA-mediated ARF1 knockdown affecting HAZV gene expression. HAZV exploitation of COPI components in a noncanonical Arf1-independent process suggests that COPI coatomer components may perform roles unrelated to vesicle formation, adding further complexity to our understanding of cargo-mediated transport. IMPORTANCE Nairoviruses are tick-borne enveloped RNA viruses that include several pathogens responsible for fatal disease in humans and animals. Here, we analyzed host genes involved in trafficking networks to examine their involvement in nairovirus replication. We revealed important roles for genes that express multiple components of the COPI complex, which regulates transport of Golgi apparatus-resident cargos. COPI components influenced at least two stages of the nairovirus replication cycle: an early stage prior to and including gene expression and also a later stage during assembly of infectious virus, with COPI knockdown reducing titers by approximately 1,000-fold. Importantly, while the late stage was Arf1 dependent, as expected for canonical COPI vesicle formation, the early stage was found to be Arf1 independent, suggestive of a previously unreported function of COPI unrelated to vesicle formation. Collectively, these data improve our understanding of nairovirus host-pathogen interactions and suggest a new Arf1-independent role for components of the COPI coatomer complex.
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- 2020
37. Hantavirus infection in type I interferon receptor-deficient (A129) mice
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Victoria A. Graham, Roger Hewson, Stephen Findlay-Wilson, Francisco J. Salguero, Stuart D. Dowall, Marilyn Aram, and Kirsty Emery
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0301 basic medicine ,Male ,Orthohantavirus ,viruses ,Hantavirus Infections ,030106 microbiology ,seoul virus ,Spleen ,Receptor, Interferon alpha-beta ,Biology ,Kidney ,Virus ,Negative-strand RNA Viruses ,03 medical and health sciences ,Mice ,In vivo ,Virology ,medicine ,Animals ,Lung ,mouse ,Hantavirus ,Mice, Knockout ,model ,Animal ,Disease Models, Animal ,Viral Tropism ,030104 developmental biology ,medicine.anatomical_structure ,Liver ,Hemorrhagic Fever with Renal Syndrome ,Knockout mouse ,RNA, Viral ,Hantavirus Infection ,Seoul virus ,Research Article - Abstract
Type I interferon receptor knockout mice (strain A129) were assessed as a disease model of hantavirus infection. A range of infection routes (intramuscular, intraperitoneal and intranasal) were assessed using minimally passaged Seoul virus (strain Humber). Dissemination of virus to the spleen, kidney and lung was observed at 5 days after intramuscular and intraperitoneal challenge, which was resolved by day 14. In contrast, intranasal challenge of A129 mice demonstrated virus tropism to the lung, which was maintained to day 14 post-challenge. These data support the use of the A129 mouse model for future infection studies and thein vivoevaluation of interventions.
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- 2020
38. A flexible format LAMP assay for rapid detection of Ebola virus
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Robert J. Watson, Andrew Bosworth, Laura C. Bonney, Roger Hewson, Nadina Wand, Gillian S. Slack, and Barry, Alyssa E
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0301 basic medicine ,Zaire ebolavirus ,RNA viruses ,Physiology ,viruses ,RC955-962 ,Artificial Gene Amplification and Extension ,Urine ,medicine.disease_cause ,Pathology and Laboratory Medicine ,Polymerase Chain Reaction ,Multiplexing ,Disease Outbreaks ,0302 clinical medicine ,Contaminants ,Arctic medicine. Tropical medicine ,False positive paradox ,Medicine and Health Sciences ,Materials ,Ebola virus RNA ,Ebolavirus ,Body Fluids ,Separation Processes ,Infectious Diseases ,Bioassays and Physiological Analysis ,Medical Microbiology ,Filoviruses ,Viral Pathogens ,Viruses ,Physical Sciences ,Telecommunications ,RNA, Viral ,Engineering and Technology ,Pathogens ,Anatomy ,Public aspects of medicine ,RA1-1270 ,Ebola Virus ,Nucleic Acid Amplification Techniques ,Research Article ,Low resource ,030231 tropical medicine ,Materials Science ,Research and Analysis Methods ,Rapid detection ,Sensitivity and Specificity ,Microbiology ,Sierra Leone ,03 medical and health sciences ,medicine ,Humans ,Molecular Biology Techniques ,Microbial Pathogens ,Colorimetric Assays ,Molecular Biology ,Distillation ,Ebola virus ,Biology and life sciences ,business.industry ,Hemorrhagic Fever Viruses ,Public Health, Environmental and Occupational Health ,Organisms ,Reverse Transcriptase-Polymerase Chain Reaction ,Hemorrhagic Fever, Ebola ,Virology ,030104 developmental biology ,Healthcare settings ,business ,Biochemical Analysis ,Limited resources - Abstract
Background The unprecedented 2013/16 outbreak of Zaire ebolavirus (Ebola virus) in West Africa has highighted the need for rapid, high-throughput and POC diagnostic assays to enable timely detection and appropriate triaging of Ebola Virus Disease (EVD) patients. Ebola virus is highly infectious and prompt diagnosis and triage is crucial in preventing further spread within community and healthcare settings. Moreover, due to the ecology of Ebola virus it is important that newly developed diagnostic assays are suitable for use in both the healthcare environment and low resource rural locations. Methodology/Principle findings A LAMP assay was successfully developed with three detection formats; a real-time intercalating dye-based assay, a real-time probe-based assay to enable multiplexing and an end-point colourimetric assay to simplify interpretation for the field. All assay formats were sensitive and specific, detecting a range of Ebola virus strains isolated in 1976–2014; with Probit analysis predicting limits of detection of 243, 290 and 75 copies/reaction respectively and no cross-detection of related strains or other viral haemorrhagic fevers (VHF’s). The assays are rapid, (as fast as 5–7.25 mins for real-time formats) and robust, detecting Ebola virus RNA in presence of minimally diluted bodily fluids. Moreover, when tested on patient samples from the 2013/16 outbreak, there were no false positives and 93–96% of all new case positives were detected, with only a failure to detect very low copy number samples. Conclusion/Significance These are a set of robust and adaptable diagnostic solutions, which are fast, easy-to-perform-and-interpret and are suitable for use on a range of platforms including portable low-power devices. They can be readily transferred to field-laboratory settings, with no specific equipment needs and are therefore ideally placed for use in locations with limited resources., Author summary This study describes the development of a set of interchangeable diagnostic assays for the detection of Ebola virus in patient samples. Each are rapid-turnaround, highly-specific (showing no detection of non-Ebola strains), sensitive and portable. These assays are ideally placed for field-use during outbreaks in low-resource countries and equally suited to use as conventional high-throughput laboratory tests. They encompass a colourimetric option with easy-to-interpret pink-to-yellow colour-change visualisation and real-time detection formats allowing the approximation of virus copy number, which helps monitoring of virus levels during infection. The inclusion of a probe-based detection method also leaves the door open for multi-pathogen detection, which could be useful for future VHF outbreaks, where the cause is unknown.
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- 2020
39. The RNA Replication Site of Tula Orthohantavirus Resides within a Remodelled Golgi Network
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John N. Barr, Katherine A Davies, Benjamin Chadwick, Jamel Mankouri, Juan Fontana, and Roger Hewson
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0301 basic medicine ,Orthohantavirus ,replication ,stress granules ,Cell ,Virus Replication ,Article ,hantavirus ,03 medical and health sciences ,symbols.namesake ,Stress granule ,Organelle ,medicine ,Golgi ,Animals ,Humans ,RNA synthesis ,factory ,lcsh:QH301-705.5 ,In Situ Hybridization, Fluorescence ,Phylogeny ,Tula virus ,Hantavirus ,030102 biochemistry & molecular biology ,biology ,General Medicine ,Golgi apparatus ,biology.organism_classification ,Cell biology ,T-Cell Intracellular Antigen-1 ,030104 developmental biology ,medicine.anatomical_structure ,lcsh:Biology (General) ,symbols ,Hantavirus Infection ,Intracellular - Abstract
The family Hantaviridae within the Bunyavirales order comprises tri-segmented negative sense RNA viruses, many of which are rodent-borne emerging pathogens associated with fatal human disease. In contrast, hantavirus infection of corresponding rodent hosts results in inapparent or latent infections, which can be recapitulated in cultured cells that become persistently infected. In this study, we used Tula virus (TULV) to investigate the location of hantavirus replication during early, peak and persistent phases of infection, over a 30-day time course. Using immunofluorescent (IF) microscopy, we showed that the TULV nucleocapsid protein (NP) is distributed within both punctate and filamentous structures, with the latter increasing in size as the infection progresses. Transmission electron microscopy of TULV-infected cell sections revealed these filamentous structures comprised aligned clusters of filament bundles. The filamentous NP-associated structures increasingly co-localized with the Golgi and with the stress granule marker TIA-1 over the infection time course, suggesting a redistribution of these cellular organelles. The analysis of the intracellular distribution of TULV RNAs using fluorescent in-situ hybridization revealed that both genomic and mRNAs co-localized with Golgi-associated filamentous compartments that were positive for TIA. These results show that TULV induces a dramatic reorganization of the intracellular environment, including the establishment of TULV RNA synthesis factories in re-modelled Golgi compartments.
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- 2020
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40. Immunogenicity and Efficacy of Zika Virus Envelope Domain III in DNA, Protein, and ChAdOx1 Adenoviral-Vectored Vaccines
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Giuditta De Lorenzo, Victoria A. Graham, Rafael A. Larocca, Jennifer Carmichael, Arvind H. Patel, Monica Poggianella, Stephen Findlay-Wilson, Cesar Lopez-Camacho, Wanwisa Dejnirattisai, Gavin R. Screaton, Emma Rayner, Arturo Reyes-Sandoval, J Slon-Campos, Young Chan Kim, Juthathip Mongkolsapaya, Dan H. Barouch, Stuart D. Dowall, Michael R. Boyd, Roger Hewson, Oscar R. Burrone, and Peter Abbink
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0301 basic medicine ,Immunogen ,viruses ,030106 microbiology ,Immunology ,lcsh:Medicine ,Viremia ,Dengue virus ,Biology ,medicine.disease_cause ,Article ,Zika virus ,03 medical and health sciences ,Antigen ,vaccine ,Drug Discovery ,medicine ,Pharmacology (medical) ,EDIII ,ZIKV ,Pharmacology ,DENV ,Immunogenicity ,lcsh:R ,adenovirus ,medicine.disease ,biology.organism_classification ,Virology ,Flavivirus ,030104 developmental biology ,Infectious Diseases ,biology.protein ,Antibody - Abstract
The flavivirus envelope protein domain III (EDIII) was an effective immunogen against dengue virus (DENV) and other related flaviviruses. Whether this can be applied to the Zika virus (ZIKV) vaccinology remains an open question. Here, we tested the efficacy of ZIKV-EDIII against ZIKV infection, using several vaccine platforms that present the antigen in various ways. We provide data demonstrating that mice vaccinated with a ZIKV-EDIII as DNA or protein-based vaccines failed to raise fully neutralizing antibodies and did not control viremia, following a ZIKV challenge, despite eliciting robust antibody responses. Furthermore, we showed that ZIKV-EDIII encoded in replication-deficient Chimpanzee adenovirus (ChAdOx1-EDIII) elicited anti-ZIKV envelope antibodies in vaccinated mice but also provided limited protection against ZIKV in two physiologically different mouse challenge models. Taken together, our data indicate that contrary to what was shown for other flaviviruses like the dengue virus, which has close similarities with ZIKV-EDIII, this antigen might not be a suitable vaccine candidate for the correct induction of protective immune responses against ZIKV.
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- 2020
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41. Characterization and applications of a Crimean-Congo hemorrhagic fever virus nucleoprotein-specific Affimer: Inhibitory effects in viral replication and development of colorimetric diagnostic tests
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Darren C. Tomlinson, John N. Barr, Paul A. Millner, Roger Hewson, Christian Tiede, Rebecca Surtees, Beatriz Álvarez-Rodríguez, John Chamberlain, Chi H. Trinh, Thomas A. Edwards, Patricia Sastre, Alba Fresco, Gillian S. Slack, Alexis C. R. Hoste, and Bird, Brian
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0301 basic medicine ,Models, Molecular ,Latex ,Molecular biology ,Protein Conformation ,RC955-962 ,Gene Expression ,Antibodies, Viral ,Virus Replication ,Biochemistry ,law.invention ,Binding Analysis ,0302 clinical medicine ,RNA interference ,law ,Arctic medicine. Tropical medicine ,Enzyme-Linked Immunoassays ,RNA structure ,Materials ,Antigens, Viral ,Crystallography ,biology ,Chemistry ,Physics ,Condensed Matter Physics ,3. Good health ,Nucleic acids ,Infectious Diseases ,Genetic interference ,Physical Sciences ,Hemorrhagic Fever Virus, Crimean-Congo ,Recombinant DNA ,Crystal Structure ,Epigenetics ,Emulsions ,Colorimetry ,Antibody ,Public aspects of medicine ,RA1-1270 ,Crimean Congo hemorrhagic fever virus ,Research Article ,030231 tropical medicine ,Materials Science ,Enzyme-Linked Immunosorbent Assay ,Research and Analysis Methods ,03 medical and health sciences ,Antigen ,Genetics ,Solid State Physics ,Animals ,Humans ,Colloids ,Immunoassays ,Chemical Characterization ,Biology and life sciences ,Diagnostic Tests, Routine ,Public Health, Environmental and Occupational Health ,Virology ,In vitro ,Nucleoprotein ,Macromolecular structure analysis ,030104 developmental biology ,Nucleoproteins ,Viral replication ,Mixtures ,Immunoglobulin G ,biology.protein ,Immunologic Techniques ,RNA ,Hemorrhagic Fever, Crimean - Abstract
Crimean-Congo hemorrhagic fever orthonairovirus (CCHFV) is one of the most widespread medically important arboviruses, causing human infections that result in mortality rates of up to 60%. We describe the selection of a high-affinity small protein (Affimer-NP) that binds specifically to the nucleoprotein (NP) of CCHFV. We demonstrate the interference of Affimer-NP in the RNA-binding function of CCHFV NP using fluorescence anisotropy, and its inhibitory effects on CCHFV gene expression in mammalian cells using a mini-genome system. Solution of the crystallographic structure of the complex formed by these two molecules at 2.84 Å resolution revealed the structural basis for this interference, with the Affimer-NP binding site positioned at the critical NP oligomerization interface. Finally, we validate the in vitro application of Affimer-NP for the development of enzyme-linked immunosorbent and lateral flow assays, presenting the first published point-of-care format test able to detect recombinant CCHFV NP in spiked human and animal sera., Author summary Crimean-Congo hemorrhagic fever virus (CCHFV) is one of the most lethal human pathogens in existence. No approved vaccine or therapies exist and rapid diagnosis of CCHFV is a critical aspect of disease management. We describe the selection and characterization of a high affinity non-antibody binding protein, Affimer-NP, that specifically recognises the CCHFV nucleocapsid protein (NP). Affimer-NP interferes with the RNA-binding function of CCHFV NP and inhibits CCHFV gene expression in mammalian cells. Solution of the crystallographic structure of the CCHFV NP/Affimer-NP complex at 2.84 Å resolution revealed the structural basis for this interference, and we validated the in vitro application of this novel molecule for the development of ELISA and lateral flow assays, presenting the first published prototype point-of-care test able to detect recombinant CCHFV NP in spiked human and animal sera. These findings present a possible starting point for the future development of anti-viral molecules targeted to CCHFV NP, and diagnostic assays for the detection of CCHFV NP, contributing to the preparedness for potential future outbreak scenarios.
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- 2020
42. A Multi-Filovirus Vaccine Candidate: Co-Expression of Ebola, Sudan, and Marburg Antigens in a Single Vector
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Stuart D. Dowall, Sarah Sebastian, Edward Wright, Sarah C. Gilbert, Hannah Sharpe, Marta Ulaszewska, Alexandra J. Spencer, Amy Flaxman, Roger Hewson, Teresa Lambe, Kuan M Cha, and Ciaran Gilbride
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0301 basic medicine ,Zaire ebolavirus ,filovirus ,Immunology ,Sudan ebolavirus ,lcsh:Medicine ,medicine.disease_cause ,Article ,Viral vector ,Marburg virus ,03 medical and health sciences ,Marburg ,0302 clinical medicine ,Immunity ,vaccine ,Drug Discovery ,medicine ,Pharmacology (medical) ,030212 general & internal medicine ,Vector (molecular biology) ,Virus classification ,Pharmacology ,biology ,viral vector ,lcsh:R ,biology.organism_classification ,Virology ,Vaccination ,030104 developmental biology ,Infectious Diseases ,Ebola - Abstract
In the infectious diseases field, protective immunity against individual virus species or strains does not always confer cross-reactive immunity to closely related viruses, leaving individuals susceptible to disease after exposure to related virus species. This is a significant hurdle in the field of vaccine development, in which broadly protective vaccines represent an unmet need. This is particularly evident for filoviruses, as there are multiple family members that can cause lethal haemorrhagic fever, including Zaire ebolavirus, Sudan ebolavirus, and Marburg virus. In an attempt to address this need, both pre-clinical and clinical studies previously used mixed or co-administered monovalent vaccines to prevent filovirus mediated disease. However, these multi-vaccine and multi-dose vaccination regimens do not represent a practical immunisation scheme when considering the target endemic areas. We describe here the development of a single multi-pathogen filovirus vaccine candidate based on a replication-deficient simian adenoviral vector. Our vaccine candidate encodes three different filovirus glycoproteins in one vector and induces strong cellular and humoral immunity to all three viral glycoproteins after a single vaccination. Crucially, it was found to be protective in a stringent Zaire ebolavirus challenge in guinea pigs in a one-shot vaccination regimen. This trivalent filovirus vaccine offers a tenable vaccine product that could be rapidly translated to the clinic to prevent filovirus-mediated viral haemorrhagic fever.
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- 2020
43. Comparison of Zaire ebolavirus realtime RT-PCRs targeting the nucleoprotein gene
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Laura Kakkola, Olli Vapalahti, Robert J. Watson, Ilkka Julkunen, Roger Hewson, Anne J. Jääskeläinen, Minttu Kaloinen, Manfred Weidmann, Tarja Sironen, Ali Mirazimi, Medicum, HUSLAB, Staff Services, Viral Zoonosis Research Unit, Department of Virology, Helsinki One Health (HOH), Emerging Infections Research Group, Veterinary Biosciences, Veterinary Microbiology and Epidemiology, and Olli Pekka Vapalahti / Principal Investigator
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0301 basic medicine ,Zaire ebolavirus ,030106 microbiology ,Biology ,medicine.disease_cause ,Rapid detection ,Polymerase Chain Reaction ,Sensitivity and Specificity ,FILOVIRUSES ,law.invention ,03 medical and health sciences ,law ,Limit of Detection ,Virology ,medicine ,Humans ,Zaire ,Gene ,Polymerase chain reaction ,Nucleoprotein ,11832 Microbiology and virology ,RAPID DETECTION ,Outbreak ,Hemorrhagic Fever, Ebola ,Nucleocapsid Proteins ,Ebolavirus ,3142 Public health care science, environmental and occupational health ,3. Good health ,PCR ,030104 developmental biology ,Molecular Diagnostic Techniques ,Ebola ,RNA, Viral - Abstract
In last five years, the Africa has faced two outbreaks of Zaire ebolavirus. These outbreaks have been the largest so far, and latest outbreak is still ongoing and affecting the Democratic Republic of the Congo. We tested in parallel three different Zaire ebolavirus (EBOV) realtime RT-PCRs targeting the nucleoprotein gene (EBOV NP-RT-qPCRs) described by Trombley et al. (2010) ; Huang et al. (2012) and Weidmann et al. (2004) . These assays are used regularly in diagnostic laboratories. The limit of detection (LOD), intra-assay repeatability using different matrixes, sensitivity and specificity were determined. In addition, the primers and probes were aligned with the sequences available in ongoing and past outbreaks in order to check the mismatches. The specificity of all three EBOV NP-RT-qPCRs were excellent (100 %), and LODs were under or 10 copies per PCR reaction. Intra-assay repeatability was good in all assays, however the Ct-values were bit higher using the EDTA-blood based matrix. All of the primers and probes in EBOV NP-RT-qPCR assays have one or more mismatches in the probes and primers when the 2267 Zaire EBOV NP sequences, including strains Ituri from DRC outbreak (year 2018), was aligned. The EBOV strain of Bikoro (year 2018) circulating in DRC was 100 % match in Trombley and Weidmann assay, but had one mismatch in Huang assay.
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- 2020
44. Towards quantification of protective antibody responses by passive transfer of the 1st WHO International Standard for Ebola virus antibody in a guinea pig model
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Stephen Findlay-Wilson, Mark Page, Sarah L. Kempster, Victoria A. Graham, Neil Almond, Roger Hewson, Stuart D. Dowall, and Giada Mattiuzzo
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Biosafety level 4 ,030231 tropical medicine ,Guinea Pigs ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Drug Development ,medicine ,Global health ,Animals ,030212 general & internal medicine ,Ebola Vaccines ,Ebola virus ,General Veterinary ,General Immunology and Microbiology ,biology ,business.industry ,Immune protection ,International standard ,Public Health, Environmental and Occupational Health ,Immunization, Passive ,Outbreak ,Hemorrhagic Fever, Ebola ,Ebolavirus ,Virology ,Infectious Diseases ,Antibody Formation ,biology.protein ,Molecular Medicine ,Female ,Protective antibody ,Antibody ,business - Abstract
Ebola virus (EBOV) represents a major concern to global health due to the unpredictable nature of outbreaks. Infection with EBOV can cause a severe viral haemorrhagic fever with no licensed vaccine or treatment, restricting work with live EBOV to Containment/Biosafety Level 4 facilities. Whilst the magnitude of recent outbreaks has provided an impetus for vaccine and antiviral development, establishing the efficacy of candidate vaccine materials relies on EBOV challenge models and advanced human trials should outbreaks occur and where logistics and funding allow. To address these hurdles in vaccine development, we investigated whether a recently established serological reference standard, the 1st WHO International Standard for Ebola virus antibody, could be used to provide a quantifiable correlate of immune protection in vivo. Dilutions of the International Standard were inoculated into naive guinea pigs 24 h before challenge with a lethal dose of Ebola virus. Only subjects receiving the highest dose of the International Standard exhibited evidence of delayed progression. Due to it being a WHO established reagent and available globally upon request, this standard allows for effective comparisons of data between laboratories and may prove valuable to select the candidate vaccines that are most likely to confer humoral immune protection ensuring the most promising candidates progress into efficacy studies.
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- 2020
45. Crimean-Congo haemorrhagic fever (CCHF) virus-specific antibody detection in blood donors, Castile-León, Spain, summer 2017 and 2018
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Nuria Leralta, María Paz Sánchez Seco, Roger Hewson, Montserrat Alonso Sardón, Fernando de Ory Manchón, Ana Jiménez del Bianco, María Belén Vicente Santiago, Rufino Alamo-Sanz, Sonia Pérez González, Ana Isabel Negredo, Moncef Belhassen-García, Isabel Bas, Juan Luis Muñoz Bellido, Lydia Blanco Peris, María Carmen Vieira Lista, Pedro Fernández Soto, Lía Monsalve Arteaga, Antonio Muro, Instituto de Salud Carlos III, and Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
- Subjects
0301 basic medicine ,Male ,Veterinary medicine ,Epidemiology ,Blood Donors ,emerging diseases ,Antibodies, Viral ,viral haemorrhagic fever ,Laboratory ,0302 clinical medicine ,Ticks ,Seroepidemiologic Studies ,Tick-borne diseases ,030212 general & internal medicine ,Animal Husbandry ,Crimean-Congo haemorrhagic fever ,Tick-borne disease ,biology ,Emerging diseases ,Middle Aged ,Specific antibody ,Hemorrhagic Fever Virus, Crimean-Congo ,epidemiology ,Female ,Antibody ,medicine.symptom ,Adult ,medicine.medical_specialty ,Blood donor ,tick-borne diseases ,re-emerging diseases ,Enzyme-Linked Immunosorbent Assay ,Asymptomatic ,Virus ,03 medical and health sciences ,Virology ,CCHF ,medicine ,Animals ,Humans ,CCHF VIRUS ,blood donor ,Viral haemorrhagic fever ,Aged ,Re-emerging diseases ,business.industry ,Research ,Public Health, Environmental and Occupational Health ,medicine.disease ,030104 developmental biology ,Cross-Sectional Studies ,Spain ,biology.protein ,Hemorrhagic Fever, Crimean ,business ,laboratory - Abstract
Background Crimean-Congo haemorrhagic fever virus (CCHFV) is considered an emerging or even a probable re-emerging pathogen in southern Europe. Presence of this virus had been reported previously in Spain in 2010. Aim We aimed to evaluate the potential circulation of CCHFV in western Spain with a serosurvey in asymptomatic adults (blood donors). Methods During 2017 and 2018, we conducted a CCHFV serosurvey in randomly selected asymptomatic blood donors from western Spain. Three assays using specific IgG antibodies against CCHFV were performed: the VectoCrimea ELISA test, an in-house ELISA and indirect immunofluorescence (EuroImmun) test with glycoprotein and nucleoprotein. Results A total of 516 blood donors participated in this cross-sectional study. The majority of the study participants were male (68.4%), and the mean age was 46.3 years. Most of the participants came from rural areas (86.8%) and 68.6% had contact with animals and 20.9% had animal husbandry practices. One in five participants (109/516, 21.1%) were engaged in at-risk professional activities such as agriculture and shepherding, slaughtering, hunting, veterinary and healthcare work (mainly nursing staff and laboratory technicians). A total of 15.3% of the participants were bitten by ticks in the days or months before the date of sampling. We detected anti-CCHFV IgG antibodies with two diagnostic assays in three of the 516 individuals and with one diagnostic assay in six of the 516 individuals. Conclusion Seroprevalence of CCHFV was between 0.58% and 1.16% in Castile-León, Spain. This is the first study in western Spain that showed circulation of CCHFV in healthy people.
- Published
- 2020
46. Emerging arboviruses of clinical importance in Central Asia
- Author
-
Roger Hewson and Barry Atkinson
- Subjects
0301 basic medicine ,Arbovirus Infections ,viruses ,Tick-borne encephalitis ,Outbreak ,Biology ,medicine.disease ,Communicable Diseases, Emerging ,Arbovirus ,Virology ,Tahyna virus ,Virus ,03 medical and health sciences ,030104 developmental biology ,Population Surveillance ,Asia, Central ,Karshi virus ,medicine ,Humans ,Arboviruses ,Arthropod Vector - Abstract
Arboviruses are viral pathogens that are transmitted from an animal reservoir to humans via an arthropod vector. These viruses result in a large burden of disease worldwide and show a propensity for establishing new endemic foci in geographically distant regions. The potential impact of arboviruses in Central Asia is unclear due to the scarcity of reports available in English; however, the collation of available data shows that numerous important human viruses are circulating in the region. Pathogens such as Crimean-Congo haemorrhagic fever virus, tick-borne encephalitis virus and Tahyna virus are likely to be responsible for numerous cases of human disease in Central Asia on an annual basis. There is evidence that pathogens such as West Nile virus and sandfly fever virus have resulted in sporadic outbreaks of human disease across the region; these events appear to be triggered by a significant change in the abundance of local arthropod vectors or events altering the contact between humans and local arthropod populations, such as conflict or natural disasters. In addition, there are several under-researched arboviruses that could result in a significant disease, including Karshi virus, Issyk-Kul virus and Syr-Darya Valley fever virus. This review provides the first comprehensive assessment of emerging arboviruses in Central Asia. Further research is required to assess the full impact of arboviruses on human health in the region and to monitor potential spread. Up-to-date information regarding arbovirus endemicity will allow for the development and distribution of rapid diagnostics, the implementation of bite-prevention strategies in at-risk areas and improved travel recommendations.
- Published
- 2018
47. Of Mice and Monkeys: Determining Protective Serological Titres in Model Zika Virus Infections
- Author
-
Claire Ham, Neil Berry, Debbie Ferguson, Stephen Findlay-Wilson, Stuart Dowall, Mark Page, Jo Hall, Giada Mattiuzzo, Victoria A. Graham, Neil Almond, Roger Hewson, and Sarah L. Kempster
- Subjects
General Materials Science ,Biology ,biology.organism_classification ,Virology ,Serology ,Zika virus - Published
- 2019
48. Point-of-care diagnostic assay for the detection of Zika virus using the recombinase polymerase amplification method
- Author
-
Laura C. Bonney, Roger Hewson, Victoria A. Graham, Robert J. Watson, and Nadina Wand
- Subjects
0301 basic medicine ,Point-of-Care Systems ,Recombinase Polymerase Amplification ,Biology ,Diagnostic tools ,Sensitivity and Specificity ,complex mixtures ,Zika virus ,03 medical and health sciences ,Zika ,0302 clinical medicine ,Virology ,Animals ,recombinase polymerase amplification ,030212 general & internal medicine ,Vector (molecular biology) ,Conserved Sequence ,Point of care ,Animal ,Transmission (medicine) ,Genetic Variation ,Reproducibility of Results ,Outbreak ,Zika Virus ,field-diagnostic ,biology.organism_classification ,Reverse transcriptase ,isothermal ,molecular detection ,Culicidae ,030104 developmental biology ,point-of-care ,RNA, Viral ,Positive-strand RNA Viruses ,Nucleic Acid Amplification Techniques ,RPA ,Research Article - Abstract
The sudden and explosive expansion of Zika virus (ZIKV) from the African continent through Oceania and culminating in the outbreak in South America has highlighted the importance of new rapid point-of-care diagnostic tools for the control and prevention of transmission. ZIKV infection has devastating consequences, such as neurological congenital malformations in infants born to infected mothers and Guillain-Barré syndrome in adults. Additionally, its potential for transmission through vector bites, as well as from person to person through blood transfusions and sexual contact, are important considerations for prompt diagnosis. Recombinase polymerase amplification (RPA), an isothermal method, was developed as an alternative field-applicable assay to PCR. Here we report the development of a novel ZIKV real-time reverse transcriptase RPA (RT-RPA) assay capable of detecting a range of different ZIKV strains from a variety of geographical locations. The ZIKV RT-RPA was shown to be highly sensitive, being capable of detecting as few as five copies of target nucleic acid per reaction, and suitable for use with a battery-operated portable device. The ZIKV RT-RPA demonstrated 100 % specificity and 83 % sensitivity in clinical samples. Furthermore, we determined that the ZIKV RT-RPA is a versatile assay that can be applied to crude samples, such as saliva and serum, and can be used as a vector surveillance tool on crude mosquito homogenates. Therefore, the developed ZIKV RT-RPA is a useful diagnostic tool that can be transferred to a resource-limited location, eliminating the need for a specialized and sophisticated laboratory environment and highly trained staff.
- Published
- 2018
49. Detection of tick-borne encephalitis virus in the UK
- Author
-
Roger Hewson, Stuart D. Dowall, and Maya Holding
- Subjects
biology ,business.industry ,encephalitis ,Ixodes ricinus ,vector-borne infections ,General Medicine ,biology.organism_classification ,Antibodies, Viral ,Virology ,United Kingdom ,Encephalitis Viruses, Tick-Borne ,zoonoses ,Tick-borne encephalitis virus ,Tick borne ,flavivirus ,Encephalitis Viruses ,Medicine ,business ,tick-borne virus ,Rapid Communication - Abstract
The presence of tick-borne encephalitis virus (TBEV) was detected in a questing tick pool in southern England in September 2019. Hitherto, TBEV had only been detected in a limited area in eastern England. This southern English viral genome sequence is distinct from TBEV-UK, being most similar to TBEV-NL. The new location of TBEV presence highlights that the diagnosis of tick-borne encephalitis should be considered in encephalitic patients in areas of the United Kingdom outside eastern England.
- Published
- 2019
50. Detection of new endemic focus of tick-borne encephalitis virus (TBEV), Hampshire/Dorset border, England, September 2019
- Author
-
Kayleigh M. Hansford, Richard Vipond, Maya Holding, Roger Hewson, Stuart D. Dowall, Jolyon M. Medlock, Steven T. Pullan, Matthew Baylis, Daniel P. Carter, John Chamberlain, Mollie Curran-French, and Liz McGinley
- Subjects
0301 basic medicine ,Tick-borne encephalitis virus TBEV ,Ixodes ricinus ,Epidemiology ,030231 tropical medicine ,Public Health, Environmental and Occupational Health ,Biology ,Tick ,medicine.disease ,biology.organism_classification ,Virology ,Virus ,03 medical and health sciences ,Flavivirus ,030104 developmental biology ,0302 clinical medicine ,medicine ,Tick-borne virus ,Encephalitis - Abstract
The presence of tick-borne encephalitis virus (TBEV) was detected in a questing tick pool in southern England in September 2019. Hitherto, TBEV had only been detected in a limited area in eastern England. This southern English viral genome sequence is distinct from TBEV-UK, being most similar to TBEV-NL. The new location of TBEV presence highlights that the diagnosis of tick-borne encephalitis should be considered in encephalitic patients in areas of the United Kingdom outside eastern England.
- Published
- 2019
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