1,498 results on '"Institute for Virus Research"'
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2. Analysis of Dominant-Negative Effects of Mutant Env Proteins of Human Immunodeficiency Virus Type 1
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Iwatani, Yasumasa, Kawano, Kumi, Ueno, Takaharu, Tanaka, Masakazu, Ishimoto, Akinori, Ito, Masahiko, and Sakai, Hiroyuki
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- 2001
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3. Th1-skewed tissue responses to a mycolyl glycolipid in mycobacteria-infected rhesus macaques
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Sugita, Masahiko [Laboratory of Cell Regulation, Institute for Virus Research, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan)]
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- 2013
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4. Factors associated with a purine-rich exonic splicing enhancer sequence in Xenopus oocyte nucleus
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Ohno, Mutsuhito [Institute for Virus Research, Kyoto University, Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan and CREST, JST (Japan)]
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- 2007
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5. Enhancement of internal ribosome entry site-mediated translation and replication of hepatitis C virus by PD98059
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Shimotohno, Kunitada [Department of Viral Oncology, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507 (Japan)]
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- 2005
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6. Roles of bHLH genes in neural stem cell differentiation
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Ohsawa, Ryosuke [Institute for Virus Research, Kyoto University, Shogoin-Kawahara, Sakyo-ku, Kyoto 606-8507 (Japan)]
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- 2005
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7. p21{sup WAF1} modulates NF-{kappa}B signaling and induces anti-apoptotic protein Bcl-2 in Tax-expressing rat fibroblast
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Shimotohno, Kunitada [Laboratory of Human Tumor Viruses, Department of Viral Oncology, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507 (Japan)]
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- 2005
- Full Text
- View/download PDF
8. Taxonomy of the order Mononegavirales: update 2018
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Kang Seuk Choi, Nikos Vasilakis, Claudio Verdugo, Janusz T. Paweska, Thomas Briese, Víctor Manuel Neira Ramírez, Andrew J. Bennett, Masayuki Horie, Charles H. Calisher, Robert Kityo, Anthony R. Fooks, Martin Schwemmle, Sunil K. Mor, Nidia G. Aréchiga Ceballos, Timothy H. Hyndman, Ayato Takada, Yíngyún Caì, Robert A. Lamb, Alexander Bukreyev, Paul A. Rota, Tony L. Goldberg, Lin-Fa Wang, Benhur Lee, Kartik Chandran, Hideki Ebihara, Michael R. Wiley, Ralf G. Dietzgen, Anna E. Whitfield, Mark D. Stenglein, Piet Maes, Andrew J. Easton, Jean L. Patterson, Valerian V. Dolja, Olga Dolnik, Eugene V. Koonin, James F. X. Wellehan, Ralf Dürrwald, Peter L. Collins, Qisheng Song, Susan Payne, Jonathan S. Towner, Sina Bavari, Sonia Vázquez-Morón, Pierre Formenty, Sophie J. Smither, Keizō Tomonaga, Leslie L. Domier, Dàohóng Jiāng, Gael Kurath, Robert B. Tesh, Sergey V. Netesov, Elodie Ghedin, Andrea Maisner, Denise A. Marston, Cristine Campos Lawson, Elke Mühlberger, Christopher F. Basler, Conrad M. Freuling, Yǒng Zhèn Zhāng, Dennis Rubbenstroth, Peter J. Walker, Gōngyín Yè, David Wang, Ron A. M. Fouchier, Gustavo Palacios, Gary P. Kobinger, Yuri I. Wolf, Timothy Song, Hideki Kondō, Mart Krupovic, Karla Prieto, David M. Stone, Luciano M. Thomazelli, Colin A. Chapman, Ashley C. Banyard, Jens H. Kuhn, Stuart G. Siddell, Noël Tordo, John M. Dye, Terry Fei Fan Ng, Charles Y. Chiu, Kim R. Blasdell, Bertus K. Rima, Victoria Wahl, Eric M. Leroy, Gaya K. Amarasinghe, Juan Emilio Echevarría, Norbert Nowotny, Roger Hewson, Thomas Müller, Viktor E. Volchkov, Washington University School of Medicine (WUSM), University of Washington [Seattle], Laboratorio de Rabia, Instituto de Diagnóstico y Referencias Epidemiológicos, Animal and Plant Health Agency [Weybridge] (APHA), Georgia State University, University System of Georgia (USG), U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), School of Veterinary Medicine, Department of Pathobiological Sciences, University of Wisconsin-Madison-Influenza Research Institute, Commonwealth Scientific and Industrial Research Organisation [Canberra] (CSIRO), Columbia Mailman School of Public Health, Columbia University [New York], The University of Texas Medical Branch (UTMB), Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, College of Veterinary Medicine and Biomedical Sciences, Colorado State University [Fort Collins] (CSU), Albert Einstein College of Medicine [New York], Department of Anthropology [Montréal], McGill University = Université McGill [Montréal, Canada], Wildlife Conservation Society (WCS), Primate Research Institute, Kyoto University, University of California [San Francisco] (UC San Francisco), University of California (UC), Avian Disease Research Division, Animal and Plant Quarantine Agency, National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Queensland Alliance for Agriculture and Food Innovation (QAAFI), University of Queensland [Brisbane], Department of Botany and Plant Pathology, Oregon State University (OSU), Center for Genome Research and Biocomputing, Philipps Universität Marburg = Philipps University of Marburg, University of Chicago, IDT Biologika, School of Life Sciences, University of Warwick [Coventry], Department of Biochemistry and Molecular Biology, University of Rochester [USA], Institute of Health Carlos III, Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Department of Viroscience [Rotterdam, The Netherlands], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Institute of Molecular Virology and Cell Biology, Federal Research Institute for Animal Health - Friedrich-Loeffler-Institut, Center for Genomics and Systems Biology, Department of Biology [New York], New York University [New York] (NYU), NYU System (NYU)-NYU System (NYU)-New York University [New York] (NYU), NYU System (NYU)-NYU System (NYU), Public Health England [Salisbury] (PHE), Kagoshima University, Murdoch University, State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University [Wuhan] (HZAU), Makerere University [Kampala, Ouganda] (MAK), Research Centre in Infectious Diseases, CHUL Research Centre and Department of Microbiology and Immunology, Université Laval [Québec] (ULaval)-Faculty of Medicine, Institute of Plant Science and Resources, Okayama University, National Center for Biotechnology Information (NCBI), Biologie Moléculaire du Gène chez les Extrêmophiles (BMGE), Institut Pasteur [Paris] (IP), US Geological Survey [Seattle], United States Geological Survey [Reston] (USGS), Northwestern University [Evanston], Icahn School of Medicine at Mount Sinai [New York] (MSSM), Centre International de Recherches Médicales de Franceville (CIRMF), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Neuromuscular Diagnostic Laboratory, University of Minnesota [Twin Cities] (UMN), University of Minnesota System-University of Minnesota System, Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Universidad de Chile = University of Chile [Santiago] (UCHILE), Novosibirsk State University (NSU), Department of Medicine [San Francisco], University of California (UC)-University of California (UC), University of Veterinary Medicine [Vienna] (Vetmeduni), Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU), Texas Biomedical Research Institute [San Antonio, TX], National Institute for Communicable Diseases [Johannesburg] (NICD), Queen's University [Belfast] (QUB), National Center for Immunization and Respiratory Diseases, CDC, Centers for Disease Control and Prevention (CDC), University of Freiburg [Freiburg], University of Bristol [Bristol], Defence Science and Technology Laboratory (Dstl), Ministry of Defence (UK) (MOD), University of Missouri [Columbia] (Mizzou), University of Missouri System, Department of Microbiology, Immunology and Pathology, Centre for Environment, Fisheries and Aquaculture Science [Weymouth] (CEFAS), Hokkaido University [Sapporo, Japan], Universidade de São Paulo - USP (BRAZIL), Institute for Virus Research, Stratégies antivirales, Institut Pasteur de Guinée, Réseau International des Instituts Pasteur (RIIP), Viral Special Pathogens Branch, Centers for Disease Control and Prevention-WHO Collaborative Centre for Viral Hemorrhagic Fevers, Facultad de Ciencias Veterinarias [Buenos Aires], Universidad de Buenos Aires [Buenos Aires] (UBA), Bases moléculaires de la pathogénicité virale – Molecular Basis of Viral Pathogenicity (BMPV), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), National Biodefense Analysis and Countermeasures Center [Frederick], U.S. Social Security Administration, CSIRO Health & Biosecurity, Department of Agriculture, Fisheries and Forestry, Ecoscience Precinct, GPO Box 267, Brisbane, Duke-NUS Medical School [Singapore], University of Florida [Gainesville] (UF), University of Nebraska Medical Center, University of Nebraska System, Kansas State University, State Key Laboratory of Rice Biology, China National Rice Research Institute, Chinese Academy of Agricultural Sciences (CAAS), State Key Laboratory for Infectious Disease prevention and Control, Beijing Institute of Technology (BIT), Army Medical Research Institute of Infectious Diseases [USA] (USAMRIID), Albert Einstein College of Medicine, McGill University, Kyoto University [Kyoto], University of California [San Francisco] (UCSF), University of California, Queensland Alliance for Agriculture and Food Innovation, University of Queensland (UQ), Philipps University of Marburg, Warwick University, Public Health England [Porton Down, Salisbury], Huazhong Agricultural University, Makerere University (MAK), Faculty of Medicine-Laval University [Québec], Okayama University [Okayama], Institut Pasteur [Paris], Centre International de Recherches Médicales de Franceville, University of Minnesota [Twin Cities], Universidad de Chile, University of California-University of California, Texas Biomedical Research Institute [San Antonio, Texas], National Institute for Communicable Diseases (NICD), Centre for Experimental Medicine [Queen’s University of Belfast], University of Bristol (School of Cellular and Molecular Medicine), University of Missouri [Columbia], Hokkaido University, Bases moléculaires de la pathogénicité virale – Molecular Basis of Viral Pathogenicity, Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Duke NUS Medical School, University of Florida [Gainesville], and Virology
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0301 basic medicine ,Order Mononegavirales ,040301 veterinary sciences ,Mononegavirales Infections ,04 agricultural and veterinary sciences ,General Medicine ,Biology ,Data science ,Virology ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,Article ,0403 veterinary science ,03 medical and health sciences ,030104 developmental biology ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Humans ,Animals ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Taxonomy (biology) ,Mononegavirales ,Phylogeny - Abstract
International audience; In 2018, the order Mononegavirales was expanded by inclusion of 1 new genus and 12 novel species. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV) and summarizes additional taxonomic proposals that may affect the order in the near future.
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- 2018
9. Taxonomy of the order Mononegavirales : update 2017
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Andrew J. Easton, Gael Kurath, Jonathan S. Towner, Qi Fang, Calogero Terregino, Noël Tordo, Jean L. Patterson, John H. Werren, John M. Dye, Andrea Maisner, Qisheng Song, Peter J. Walker, Benhur Lee, Pierre Formenty, Richard E. Randall, Ralf Dürrwald, Kim R. Blasdell, Alisa Bochnowski, Bertus K. Rima, Robert A. Lamb, Paul A. Rota, Kartik Chandran, Ralf G. Dietzgen, David M. Stone, Norbert Nowotny, Hideki Kondo, Roger Hewson, Anna E. Whitfield, Janusz T. Paweska, Masayuki Horie, Peter L. Collins, Keizo Tomonaga, Martin Schwemmle, Anthony P. James, Olga Dolnik, Gary P. Kobinger, Beibei Wang, Michael N. Pearson, Nicolás Bejerman, Susan Payne, Ming Li, Jian Hong, Fei Wang, Christopher F. Basler, Robert M. Harding, Jens H. Kuhn, Ron A. M. Fouchier, Charles H. Calisher, Eric M. Leroy, Viktor E. Volchkov, Hideki Ebihara, Lin-Fa Wang, Dàohóng Jiāng, Sina Bavari, Gaya K. Amarasinghe, Ayato Takada, Sergey V. Netesov, Elke Mühlberger, Sophie J. Smither, David Wang, Gongyin Ye, Peter Revill, Martin Beer, Colleen M. Higgins, Yīmíng Bào, Robert B. Tesh, Victoria Wahl-Jensen, Thomas Briese, Zhichao Yan, Dennis Rubbenstroth, Elodie Ghedin, Alexander Bukreyev, Nikos Vasilakis, Virology, Washington University School of Medicine (WUSM), University of Washington [Seattle], National Center for Biotechnology Information (NCBI), Georgia State University, University System of Georgia (USG), Army Medical Research Institute of Infectious Diseases [USA] (USAMRIID), Institute of Diagnostic Virology (IVD), Friedrich-Loeffler-Institut (FLI), Instituto Nacional de Tecnología Agropecuaria, Universidad Nacional de la Patagonia Austral (UNPA), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), Commonwealth Scientific and Industrial Research Organisation [Canberra] (CSIRO), Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Columbia Mailman School of Public Health, The University of Texas Medical Branch (UTMB), College of Veterinary Medicine and Biomedical Sciences, Colorado State University [Fort Collins] (CSU), Albert Einstein College of Medicine [New York], National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Queensland Alliance for Agriculture and Food Innovation (QAAFI), University of Queensland [Brisbane], Philipps University of Marburg, IDT Biologika, School of Life Sciences, Warwick University, Department of Biochemistry and Molecular Biology, University of Rochester [USA], State Key Laboratory of Rice Biology, China National Rice Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Department of Viroscience [Rotterdam, The Netherlands], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Center for Genomics and Systems Biology, Department of Biology [New York], New York University [New York] (NYU), NYU System (NYU)-NYU System (NYU)-New York University [New York] (NYU), NYU System (NYU)-NYU System (NYU), Centre for Tropical Crops and Biocommodities, Queensland University of Technology, Public Health England [Salisbury] (PHE), Auckland University of Technology (AUT), Infections Virales et Pathologie Comparée - UMR 754 (IVPC), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Kagoshima University, State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Research Centre in Infectious Diseases, CHUL Research Centre and Department of Microbiology and Immunology, Université Laval [Québec] (ULaval)-Faculty of Medicine, Institute of Plant Science and Resources, Okayama University, US Geological Survey [Seattle], United States Geological Survey [Reston] (USGS), Northwestern University [Evanston], Icahn School of Medicine at Mount Sinai [New York] (MSSM), Centre International de Recherches Médicales de Franceville (CIRMF), Institute for Applied Ecology New Zealand (AENZ), Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Novosibirsk State University (NSU), University of Veterinary Medicine [Vienna] (Vetmeduni), Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU), Texas Biomedical Research Institute [San Antonio, TX], Texas A&M University System, National Institute for Communicable Diseases [Johannesburg] (NICD), University of Auckland [Auckland], Biomedical Sciences Research Complex [St Andrews, Scotland] (BSRC), University of St Andrews [Scotland], Victorian Infectious Diseases Reference Laboratory, Queen's University [Belfast] (QUB), National Center for Immunization and Respiratory Diseases, CDC, Centers for Disease Control and Prevention (CDC), University of Freiburg [Freiburg], Defence Science and Technology Laboratory (Dstl), Ministry of Defence (UK) (MOD), University of Missouri School of Medicine, University of Missouri System, Centre for Environment, Fisheries and Aquaculture Science [Weymouth] (CEFAS), Hokkaido University [Sapporo, Japan], Istituto Zooprofilattico Sperimentale delle Venezie (IZSVe), Institute for Virus Research, Kyoto University [Kyoto], Stratégies antivirales, Institut Pasteur [Paris], Institut Pasteur de Guinée, Réseau International des Instituts Pasteur (RIIP), Viral Special Pathogens Branch, Centers for Disease Control and Prevention-WHO Collaborative Centre for Viral Hemorrhagic Fevers, Bases moléculaires de la pathogénicité virale – Molecular Basis of Viral Pathogenicity (BMPV), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), National Biodefense Analysis and Countermeasures Center [Frederick], U.S. Social Security Administration, CSIRO Health & Biosecurity, Washington University School of Medicine, Department of Agriculture, Fisheries and Forestry, Ecoscience Precinct, GPO Box 267, Brisbane, Duke-NUS Medical School [Singapore], Department of Biology, Kansas State University, Albert Einstein College of Medicine, Queensland Alliance for Agriculture and Food Innovation, University of Queensland (UQ), Public Health England [Porton Down, Salisbury], Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE)-Université Claude Bernard Lyon 1 (UCBL), Faculty of Medicine-Laval University [Québec], Okayama University [Okayama], Centre International de Recherches Médicales de Franceville, Institute for Applied Ecology New Zealand, Texas Biomedical Research Institute [San Antonio, Texas], A&M University, National Institute for Communicable Diseases (NICD), The University of Auckland, Centre for Experimental Medicine [Queen’s University of Belfast], Hokkaido University, Istituto Zooprofilattico Sperimentale delle Venezie, Bases moléculaires de la pathogénicité virale – Molecular Basis of Viral Pathogenicity, Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Duke NUS Medical School, U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Columbia University [New York], Philipps Universität Marburg = Philipps University of Marburg, University of Warwick [Coventry], Queensland University of Technology [Brisbane] (QUT), Institut National de la Recherche Agronomique (INRA)-École Pratique des Hautes Études (EPHE), Huazhong Agricultural University [Wuhan] (HZAU), Victorian Infectious Diseases Reference Laboratory [Melbourne, Australia] (VIDRL), Kyoto University, Institut Pasteur [Paris] (IP), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Biomedical Sciences Research Complex
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0301 basic medicine ,030106 microbiology ,Genome, Viral ,Article ,03 medical and health sciences ,Species Specificity ,Genus ,Phylogenetics ,Virology ,Gene Order ,Viral ,Mononegavirales ,Phylogeny ,Order Mononegavirales ,Genome ,biology ,General Medicine ,Pneumovirus ,biology.organism_classification ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,030104 developmental biology ,Evolutionary biology ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Taxonomy (biology) - Abstract
International audience; In 2017, the order Mononegavirales was expanded by the inclusion of a total of 69 novel species. Five new rhabdovirus genera and one new nyamivirus genus were established to harbor 41 of these species, whereas the remaining new species were assigned to already established genera. Furthermore, non-Latinized binomial species names replaced all paramyxovirus and pneumovirus species names, thereby accomplishing application of binomial species names throughout the entire order. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV).
- Published
- 2017
10. Taxonomy of the order Mononegavirales: update 2016
- Author
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Ralf Dürrwald, Krisztián Bányai, Robert A. Lamb, Hideki Kondo, Alexander Bukreyev, Anna N. Clawson, Calogero Terregino, Robert B. Tesh, Andrew J. Easton, Andrea Maisner, Paul A. Rota, Gael Kurath, Kartik Chandran, Charles H. Calisher, Ralf G. Dietzgen, Janusz T. Paweska, Szilvia Marton, Dennis Rubbenstroth, Masayuki Horie, Juliana Freitas-Astúa, Bertus K. Rima, Jonathan S. Towner, Viktor E. Volchkov, Eric M. Leroy, David M. Stone, Susan Payne, Kwok-Yung Yuen, Hideki Ebihara, Lin-Fa Wang, Lìjiāng Liú, C. Li, Nikos Vasilakis, Olga Dolnik, Gaya K. Amarasinghe, Gary P. Kobinger, Jean L. Patterson, Sergio Lenardon, Xian Dan Lin, Leslie L. Domier, Mang Shi, Pierre Formenty, Ben Longdon, Anna E. Whitfield, Sina Bavari, Timothy H. Hyndman, Martin Verbeek, E. W. Kitajima, Elke Mühlberger, Peter J. Walker, Ayato Takada, Mark D. Stenglein, François Xavier Briand, David Wang, Elodie Ghedin, Jiāsēn Chéng, Keizo Tomonaga, Norbert Nowotny, Roger Hewson, Noël Tordo, Jun Hua Tian, Nicolás Bejerman, John M. Dye, Christopher F. Basler, Yong-Zhen Zhang, Kim R. Blasdell, Yanping Fu, Sophie J. Smither, Richard E. Randall, Jens H. Kuhn, Jiǎtāo Xiè, Victoria Wahl-Jensen, Thierry Wetzel, Martin Schwemmle, Michael M. Goodin, John A. Walsh, Thomas Briese, Yīmíng Bào, Peter L. Collins, Dàohóng Jiāng, Sergey V. Netesov, Ron A. M. Fouchier, Szilvia L. Farkas, Claudio L. Afonso, US Department of Agriculture, Washington University School of Medicine (WUSM), University of Washington [Seattle], Centre for Agricultural Research [Budapest] (ATK), Hungarian Academy of Sciences (MTA), National Center for Biotechnology Information (NCBI), Georgia State University, University System of Georgia (USG), Army Medical Research Institute of Infectious Diseases [USA] (USAMRIID), Instituto Nacional de Tecnología Agropecuaria, Universidad Nacional de la Patagonia Austral (UNPA), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), Commonwealth Scientific and Industrial Research Organisation [Canberra] (CSIRO), Laboratoire de Ploufragan-Plouzané-Niort [ANSES], Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Columbia Mailman School of Public Health, The University of Texas Medical Branch (UTMB), Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University System, Albert Einstein College of Medicine [New York], Huazhong Agricultural University, Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Queensland Alliance for Agriculture and Food Innovation - Centre for Animal Science, University of Queensland [Brisbane], Philipps University of Marburg, University of Illinois [Chicago] (UIC), University of Illinois System, IDT Biologika, School of Life Sciences, Warwick University, Laboratory of Persistent Viral Diseases, LABOKLIN, Embrapa Cassava and Fruits, Brazilian Agricultural Research Corporation (Embrapa), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Department of Viroscience [Rotterdam, The Netherlands], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Center for Genomics and Systems Biology, Department of Biology [New York], New York University [New York] (NYU), NYU System (NYU)-NYU System (NYU)-New York University [New York] (NYU), NYU System (NYU)-NYU System (NYU), Department of Plant Pathology, University of Kentucky, University of Kentucky, Public Health England [Salisbury] (PHE), Kagoshima University, School of Veterinary and Life Sciences [Murdoch], Murdoch University, State Key Laboratory of Agricultural Microbiology, Escola Superior de Agricultura 'Luiz de Queiroz' (ESALQ), Universidade de São Paulo (USP), Research Centre in Infectious Diseases, CHUL Research Centre and Department of Microbiology and Immunology, Université Laval [Québec] (ULaval)-Faculty of Medicine, Institute of Plant Science and Resources, Okayama University, US Geological Survey [Seattle], United States Geological Survey [Reston] (USGS), Northwestern University [Evanston], Centre International de Recherches Médicales de Franceville (CIRMF), State Key Laboratory for Infectious Disease prevention and Control, Beijing Institute of Technology (BIT), Wēnzhōu Center for Disease Control and Prevention, Department of Genetics University of Cambridge, University of Cambridge [UK] (CAM), Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Novosibirsk State University (NSU), University of Veterinary Medicine [Vienna] (Vetmeduni), Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU), Texas Biomedical Research Institute [San Antonio, TX], College of Veterinary Medicine and Biomedical Sciences, National Institute for Communicable Diseases [Johannesburg] (NICD), Biomedical Sciences Research Complex [St Andrews, Scotland] (BSRC), University of St Andrews [Scotland], Queen's University [Belfast] (QUB), National Center for Immunization and Respiratory Diseases, CDC, Centers for Disease Control and Prevention (CDC), University of Freiburg [Freiburg], Chinese Center for Disease Control and Prevention, Defence Science and Technology Laboratory (Dstl), Ministry of Defence (UK) (MOD), Department of Microbiology, Immunology and Pathology, Colorado State University [Fort Collins] (CSU), Centre for Environment, Fisheries and Aquaculture Science [Weymouth] (CEFAS), Hokkaido University [Sapporo, Japan], Istituto Zooprofilattico Sperimentale delle Venezie (IZSVe), Wǔhàn Center for Disease Control and Prevention, Institute for Virus Research, Kyoto University [Kyoto], Stratégies antivirales, Institut Pasteur [Paris], Institut Pasteur de Guinée, Réseau International des Instituts Pasteur (RIIP), Viral Special Pathogens Branch, Centers for Disease Control and Prevention-WHO Collaborative Centre for Viral Hemorrhagic Fevers, Wageningen University and Research [Wageningen] (WUR), Bases moléculaires de la pathogénicité virale – Molecular Basis of Viral Pathogenicity (BMPV), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), National Biodefense Analysis and Countermeasures Center [Frederick], U.S. Social Security Administration, CSIRO Health & Biosecurity, Departments of Molecular Microbiology and Pathology & Immunology, Department of Agriculture, Fisheries and Forestry, Ecoscience Precinct, GPO Box 267, Brisbane, Duke-NUS Medical School [Singapore], Kansas State University, State Key Laboratory of Emerging Infectious Diseases & Department of Microbiology, The University of Hong Kong (HKU)-Li Ka Shing Faculty of Medicine, State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong (HKU), French Agency for Food, Environmental and Occupational Health & Safety (Anses) - Veterinary epidemiology, Albert Einstein College of Medicine, Public Health England [Porton Down, Salisbury], Faculty of Medicine-Laval University [Québec], Okayama University [Okayama], Centre International de Recherches Médicales de Franceville, Texas Biomedical Research Institute [San Antonio, Texas], A&M University, National Institute for Communicable Diseases (NICD), Centre for Experimental Medicine [Queen’s University of Belfast], Hokkaido University, Istituto Zooprofilattico Sperimentale delle Venezie [Padova], Wageningen University and Research Centre [Wageningen] (WUR), Bases moléculaires de la pathogénicité virale – Molecular Basis of Viral Pathogenicity, Duke NUS Medical School, U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Columbia University [New York], Huazhong Agricultural University [Wuhan] (HZAU), Philipps Universität Marburg = Philipps University of Marburg, University of Warwick [Coventry], University of Kentucky (UK), Universidade de São Paulo = University of São Paulo (USP), Kyoto University, Institut Pasteur [Paris] (IP), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Virology, and Biomedical Sciences Research Complex
- Subjects
0301 basic medicine ,030106 microbiology ,Zoology ,Genome, Viral ,Article ,03 medical and health sciences ,Genus ,Phylogenetics ,Virology ,Crustavirus ,Life Science ,Viral ,Mononegavirales ,Phylogeny ,Order Mononegavirales ,QR355 ,Genome ,biology ,Entomology & Disease Management ,General Medicine ,biology.organism_classification ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,Pneumoviridae ,Subfamily Pneumovirinae ,MONONEGAVIRALES ,030104 developmental biology ,Evolutionary biology ,Wildlife Ecology and Conservation ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Taxonomy (biology) ,RA ,RC - Abstract
International audience; In 2016, the order Mononegavirales was emended through the addition of two new families (Mymonaviridae and Sunviridae), the elevation of the paramyxoviral subfamily Pneumovirinae to family status (Pneumoviridae), the addition of five free-floating genera (Anphevirus, Arlivirus, Chengtivirus, Crustavirus, and Wastrivirus), and several other changes at the genus and species levels. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV).
- Published
- 2016
11. Sphingomyelin Activates Hepatitis C Virus RNA Polymerase in a Genotype-Specific Manner
- Author
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Koichi Watashi, Tetsuya Toyoda, Michinori Kohara, Kunitada Shimotohno, Yuichi Hirata, Masaaki Arai, Takaji Wakita, Ying He, Leiyun Weng, Jin Zhong, Key Laboratory of Molecular Virology & Immunology (LMVI), Institut Pasteur de Shanghai, Académie des Sciences de Chine - Chinese Academy of Sciences (IPS-CAS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Biology, Japan, Pharmacology Laboratory, Pharmacology Department V, Mitsubishi Tanabe Pharma Corporation, Department of Virology II, National Institute of Infectious Diseases [Tokyo], Laboratory of Human Tumor Viruses, Department of Viral Oncology, Institute for Virus Research, Kyoto University [Kyoto], and Chiba Institute of Technology (CIT)
- Subjects
viruses ,MESH: Protein Structure, Secondary ,Hepacivirus ,MESH: Sphingomyelins ,Virus Replication ,Protein Structure, Secondary ,MESH: Genotype ,MESH: Protein Structure, Tertiary ,chemistry.chemical_compound ,RNA polymerase ,MESH: Hepacivirus ,Replicon ,Lipid raft ,Polymerase ,0303 health sciences ,biology ,030302 biochemistry & molecular biology ,Hepatitis C ,Virus-Cell Interactions ,Sphingomyelins ,3. Good health ,Biochemistry ,lipids (amino acids, peptides, and proteins) ,MESH: RNA Replicase ,Sphingomyelin ,Protein Binding ,Binding domain ,MESH: Enzyme Activation ,Genotype ,Molecular Sequence Data ,Immunology ,RNA-dependent RNA polymerase ,Microbiology ,Viral Proteins ,03 medical and health sciences ,Species Specificity ,Virology ,MESH: Protein Binding ,MESH: Species Specificity ,NS5B ,030304 developmental biology ,MESH: Hepatitis C ,MESH: Molecular Sequence Data ,MESH: Virus Replication ,RNA-Dependent RNA Polymerase ,MESH: Viral Proteins ,Molecular biology ,Protein Structure, Tertiary ,carbohydrates (lipids) ,Enzyme Activation ,chemistry ,Insect Science ,biology.protein - Abstract
Hepatitis C virus (HCV) replication and infection depend on the lipid components of the cell, and replication is inhibited by inhibitors of sphingomyelin biosynthesis. We found that sphingomyelin bound to and activated genotype 1b RNA-dependent RNA polymerase (RdRp) by enhancing its template binding activity. Sphingomyelin also bound to 1a and JFH1 (genotype 2a) RdRps but did not activate them. Sphingomyelin did not bind to or activate J6CF (2a) RdRp. The sphingomyelin binding domain (SBD) of HCV RdRp was mapped to the helix-turn-helix structure (residues 231 to 260), which was essential for sphingomyelin binding and activation. Helix structures (residues 231 to 241 and 247 to 260) are important for RdRp activation, and 238S and 248E are important for maintaining the helix structures for template binding and RdRp activation by sphingomyelin. 241Q in helix 1 and the negatively charged 244D at the apex of the turn are important for sphingomyelin binding. Both amino acids are on the surface of the RdRp molecule. The polarity of the phosphocholine of sphingomyelin is important for HCV RdRp activation. However, phosphocholine did not activate RdRp. Twenty sphingomyelin molecules activated one RdRp molecule. The biochemical effect of sphingomyelin on HCV RdRp activity was virologically confirmed by the HCV replicon system. We also found that the SBD was the lipid raft membrane localization domain of HCV NS5B because JFH1 (2a) replicon cells harboring NS5B with the mutation A242C/S244D moved to the lipid raft while the wild type did not localize there. This agreed with the myriocin sensitivity of the mutant replicon. This sphingomyelin interaction is a target for HCV infection because most HCV RdRps have 241Q.
- Published
- 2010
12. Hopf bifurcation in the presomitic mesoderm during the mouse segmentation
- Author
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Aitor González, Ryoichiro Kageyama, Spinelli, Lionel, Institute for Virus Research, and Kyoto University
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Statistics and Probability ,Fibroblast Growth Factor 8 ,Notch signaling pathway ,Down-Regulation ,Biology ,Fibroblast growth factor ,General Biochemistry, Genetics and Molecular Biology ,Mesoderm ,LFNG ,Mice ,FGF8 ,Basic Helix-Loop-Helix Transcription Factors ,Morphogenesis ,medicine ,Paraxial mesoderm ,Animals ,Computer Simulation ,Receptor, Fibroblast Growth Factor, Type 1 ,Enhancer ,ComputingMilieux_MISCELLANEOUS ,[INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM] ,Mice, Knockout ,Genetics ,Receptors, Notch ,General Immunology and Microbiology ,Applied Mathematics ,Fibroblast growth factor receptor 1 ,fungi ,General Medicine ,Cell biology ,Somite ,Phenotype ,medicine.anatomical_structure ,Modeling and Simulation ,Mutation ,[INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM] ,General Agricultural and Biological Sciences ,Signal Transduction - Abstract
Vertebrae and ribs arise from embryonic tissues called somites. Somites arise sequentially from the unsegmented embryo tail, called presomitic mesoderm (PSM). The pace of somite formation is controlled by gene products such as hairy and enhancer of split 7 (Hes7) whose expression oscillates in the PSM. In addition to the cyclic genes, there is a gradient of fibroblast growth factor 8 (Fgf8) mRNA from posterior to anterior PSM. Recent experiments have shown that in the absence of Fgf signaling, Hes7 oscillations in the anterior and posterior PSM are lost. On the other hand, Notch mutants reduce the amplitude of posterior Hes7 oscillations and abolish anterior Hes7 oscillations. To understand these phenotypes, we delineated and simulated a logical and a delay differential equation (DDE) model with similar network topology in wild-type and mutant situations. Both models reproduced most wild-type and mutant phenotypes suggesting that the chosen topology is robust to explain these phenotypes. Numerical continuation of the model showed that even in the wild-type situation, the system changed from sustained to damped, i.e. a Hopf bifurcation occurred, when the Fgf concentration decreased in the PSM. This numerical continuation analysis further indicated that the most sensitive parameters for the oscillations are the parameters of Hes7 followed by those of Lunatic fringe (Lfng) and Notch1. In the wild-type, the damping of Hes7 oscillations was not so strong so that cells reached the new somites before they lose Hes7 oscillations. By contrast, in the fibroblast growth factor receptor 1 (Fgfr1) conditional knock-out (cKO) mutant simulation, Notch signaling was not able to maintain sustained Hes7 oscillations. Our analysis suggests that Fgf signaling makes cells enter an oscillatory state of Hes7 expression. After moving to the anterior PSM, where Fgf signaling is missing, Notch signaling compensates the damping of Hes7 oscillations in the anterior PSM.
- Published
- 2009
13. APH-2 and Tax expression are correlated with a HTLV-2 proviral load but not with lymphocytosis
- Author
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Paola Miyazato, Estelle Douceron, Zhanna Kaidarova, Masao Matsuoka, Renaud Mahieux, Edward L. Murphy, BMC, Ed., Virologie humaine, École normale supérieure - Lyon (ENS Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Blood Systems Research Institute, University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), Laboratory of Virus Immunology, Kyoto University-Institute for Virus Research, and École normale supérieure de Lyon (ENS de Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM)
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biology ,Lymphocytosis ,Cell growth ,T cell ,Lymphocyte ,T-cell leukemia ,medicine.disease ,Virology ,Lymphoma ,Infectious Diseases ,medicine.anatomical_structure ,In vivo ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,hemic and lymphatic diseases ,Meeting Abstract ,biology.protein ,medicine ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Antibody ,medicine.symptom ,ComputingMilieux_MISCELLANEOUS - Abstract
The recent discovery of HBZ, an antisense protein, encoded by HTLV-1 allowed a new way of understanding how HTLV-1 induces the development of adult T cell leukemia/lymphoma (ATLL). HBZ mRNA is expressed in all HTLV-1 patients tested regardless of their clinical status. Furthermore HBZ mRNA level is positively correlated to the HTLV-1 proviral load and it involved in infected T cell proliferation. The HTLV-2 homolog of HBZ, APH-2, also represses the viral transcription from the 5’ LTR. We therefore quantified APH-2 and Tax mRNA levels as well as proviral load in a series of 51 blood samples obtained from the HTLV Outcomes Study (HOST) cohort. These samples were divided in low, intermediate and high proviral load (PVL) groups. We first show that APH-2 was expressed in most (94%) samples, while Tax was expressed mostly in the high PVL group. A positive correlation was observed between PVL and Tax and between PVL and APH-2. Although lymphocytosis is commonly observed among HTLV-2 carriers, we also demonstrate that APH2, contrary to HBZ does not promote cell proliferation in vitro. These results were confirmed in vivo since we did not observe a correlation between APH-2 level and the lymphocyte count. Our results therefore demonstrate that APH-2 is frequently expressed in vivo in HTLV-2 carriers. However, and contrary to HBZ, APH2 does not promote cell proliferation.
- Published
- 2011
14. HBZ is an immunogenic protein, but not a target antigen for human T-cell leukemia virus type 1-specific cytotoxic T lymphocytes
- Author
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Tadashi Matsumoto, Hiroshi Fujiwara, Taiji Ogawa, Koichiro Suemori, Jean-Michel Mesnard, Masao Matsuoka, Masaki Yasukawa, Toshiki Ochi, Ehime University Graduate School of Medecine, Institute for Virus Research, Kyoto University [Kyoto], Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and collaboration
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Leukemia, T-Cell ,MESH: Cell Line, Tumor ,medicine.medical_treatment ,viruses ,Retroviridae Proteins ,Clone (cell biology) ,chemical and pharmacologic phenomena ,MESH: Cytotoxicity Tests, Immunologic ,Biology ,MESH: Basic-Leucine Zipper Transcription Factors ,Viral Proteins ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,immune system diseases ,Cell Line, Tumor ,Virology ,hemic and lymphatic diseases ,medicine ,Humans ,Cytotoxic T cell ,Antigens, Viral ,030304 developmental biology ,Human T-lymphotropic virus 1 ,0303 health sciences ,MESH: Human T-lymphotropic virus 1 ,MESH: Humans ,hemic and immune systems ,T lymphocyte ,Immunotherapy ,Cytotoxicity Tests, Immunologic ,medicine.disease ,MESH: Viral Proteins ,3. Good health ,Leukemia ,CTL ,Basic-Leucine Zipper Transcription Factors ,Cell culture ,030220 oncology & carcinogenesis ,Immunology ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,MESH: Antigens, Viral ,MESH: T-Lymphocytes, Cytotoxic ,T-Lymphocytes, Cytotoxic ,MESH: Leukemia, T-Cell - Abstract
International audience; Recently, HBZ has been reported to play an important role in the proliferation of adult T-cell leukaemia (ATL) cells and might be a target of novel therapy for ATL. To develop a novel immunotherapy for ATL, we verified the feasibility of cellular immunotherapy targeting HBZ. We established an HBZ-specific and HLA-A*0201-restricted cytotoxic T lymphocyte (CTL) clone. Detailed study using this CTL clone clearly showed that HBZ is certainly an immunogenic protein recognizable by human CTLs; however, HBZ-specific CTLs could not lyse ATL cells. Failure of HBZ-specific CTLs to recognize human T-cell leukemia virus type 1 (HTLV-1)-infected cells might be due to a low level of HBZ protein expression in ATL cells and resistance of HTLV-1-infected cells to CTL-mediated cytotoxicity. Although HBZ plays an important role in the proliferation of HTLV-1-infected cells, it may also provide a novel mechanism that allows them to evade immune recognition.
- Published
- 2009
15. Logical modelling of the role of the Hh pathway in the patterning of the Drosophila wing disc
- Author
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Claudine Chaouiya, Aitor González, Denis Thief, Institute for Virus Research, Kyoto University, Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), and Kyoto University [Kyoto]
- Subjects
Statistics and Probability ,Patched ,Cellular differentiation ,Biology ,Bioinformatics ,Biochemistry ,Models, Biological ,03 medical and health sciences ,0302 clinical medicine ,Transcriptional regulation ,Animals ,Drosophila Proteins ,Wings, Animal ,Logical data model ,Computer Simulation ,Hedgehog Proteins ,Molecular Biology ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,Boundary cell ,Body Patterning ,0303 health sciences ,biology.organism_classification ,Computer Science Applications ,Computational Mathematics ,Imaginal disc ,Logistic Models ,Computational Theory and Mathematics ,Drosophila ,Drosophila melanogaster ,[INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM] ,Neuroscience ,030217 neurology & neurosurgery ,Morphogen ,Signal Transduction - Abstract
Motivations: The development of most tissues and organs relies on a limited number of signal transduction pathways enabling the coordination of cellular differentiation. A proper understanding of the roles of signal transduction pathways requires the definition of formal models capturing the main qualitative features of these patterning processes. This is a challenging task because the underlying processes, diffusion, regulatory modifications, reception and sequestration of signalling molecules, transcriptional regulation of target genes, etc. are only partly characterized. In this context, qualitative models can be more readily proposed on the basis of available (molecular) genetic data. But this requires novel computational tools and proper qualitative representations of phenomena such as diffusion or sequestration. To assess the power and limits of a logical formalism in this context, we propose a multi-level model of the multi-cellular network involved in the definition of the anterior–posterior boundary during the development of the wing disc of Drosophila melanogaster. The morphogen Hedgehog (Hh) is the inter-cellular signal coordinating this process. It diffuses from the posterior compartment of the disc to activate its pathway in cells immediately anterior to the boundary. In these boundary cells, the Hh gradient induces target genes in distinct domains as a function of the Hh concentration. One target of Hh signalling is the gene coding for the receptor Patched (Ptc), which sequesters Hh and impedes further diffusion, thereby refining the boundary. Results: We have delineated a logical model of the patterning process defining the cellular anterior–posterior boundary in the developing imaginal disc of Drosophila melanogaster. This model qualitatively accounts for the formation of a gradient of Hh, as well as for the transduction of this signal through a balance between the activatory (CiA) and inhibitory (CiR) products of the gene cubitus interruptus (ci). Wild-type and mutant simulations have been carried out to assess the coherence of the model with experimental data. Interestingly, our computational analysis provides novel insights into poorly understood processes such as the regulation of Ptc by CiR, the formation of a functional gradient of CiA across boundary cells, or yet functional En differences between anterior and posterior cells. In conclusion, our model analysis demonstrates the flexibility of the logical formalism, enabling consistent qualitative representation of diffusion, sequestration and post-transcriptional regulatory processes within and between neighbouring cells. Availability: An XML file containing the proposed model together with annotations can be downloaded from our website (http://gin.univ-mrs.fr/GINsim/), along with GINsim, a logical modelling and simulation software freely available to academic groups. Contact: thieffry@tagc.univ-mrs.fr
- Published
- 2008
16. Possibility and Challenges of Conversion of Current Virus Species Names to Linnaean Binomials
- Author
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Sbina Bavari, Susan Payne, Alexander Bukreyev, Arvind Varsani, Víctor Romanowski, Kartik Chandran, Ralf G. Dietzgen, Mark D. Stenglein, Anna N. Clawson, Sead Sabanadzovic, Gael Kurath, Andrea Maisner, Peter J. Walker, Ralf Dürrwald, Juan Carlos de la Torre, Eric M. Leroy, Mária Benko, Keizo Tomonaga, Gary P. Kobinger, Robert A. Lamb, Hideki Kondo, F. Murilo Zerbini, Martin Schwemmle, Robert B. Tesh, Gaya K. Amarasinghe, Andrew J. Easton, Michael J. Buchmeier, Jean-Paul Gonzalez, Anna E. Whitfield, Nikos Vasilakis, Jonathan S. Towner, Pierre Formenty, Jens H. Kuhn, Norbert Nowotny, Roger Hewson, Ayato Takada, Mart Krupovic, Igor S. Lukashevich, David M. Stone, Clarence J. Peters, Sheli R. Radoshitzky, Bertus K. Rima, Janusz T. Paweska, Masayuki Horie, Christopher S. Clegg, Victoria Wahl-Jensen, Christopher F. Basler, Sébastian Emonet, Charles H. Calisher, Lin-Fa Wang, Rémi N. Charrel, Jean L. Patterson, Elodie Ghedin, Dennis Rubbenstroth, Dàohóng Jiāng, Sergey V. Netesov, Hélène Sanfaçon, Thomas S. Postler, Ron A. M. Fouchier, Peter L. Collins, Noël Tordo, Maria S. Salvato, John M. Dye, Arcady Mushegian, Sophie J. Smither, Joseph L. DeRisi, Olga Dolnik, Kim R. Blasdell, Balázs Harrach, Viktor E. Volchkov, Thomas Briese, Andrew M. Kropinski, Columbia University College of Physicians and Surgeons, Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Washington University School of Medicine (WUSM), University of Washington [Seattle], Georgia State University, University System of Georgia (USG), Army Medical Research Institute of Infectious Diseases [USA] (USAMRIID), Institute for Soil Sciences and Agricultural Chemistry (ATK TAKI), Centre for Agricultural Research [Budapest] (ATK), Hungarian Academy of Sciences (MTA)-Hungarian Academy of Sciences (MTA), Commonwealth Scientific and Industrial Research Organisation [Canberra] (CSIRO), Columbia Mailman School of Public Health, University of California [Irvine] (UCI), University of California, The University of Texas Medical Branch (UTMB), College of Veterinary Medicine and Biomedical Sciences, Colorado State University [Fort Collins] (CSU), Albert Einstein College of Medicine [New York], Emergence des Pathologies Virales (EPV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Les Mandinaux, National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Department of Immunology and Microbial Science, Scripps Research Institute, Department of Medicine [San Francisco], University of California [San Francisco] (UCSF), University of California-University of California, Queensland Alliance for Agriculture and Food Innovation (QAAFI), University of Queensland [Brisbane], Philipps University of Marburg, IDT Biologika, School of Life Sciences, Warwick University, Unité de Virologie, Institut de Recherche Biomédicale des Armées (IRBA), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Department of Viroscience [Rotterdam, The Netherlands], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Center for Genomics and Systems Biology, Department of Biology [New York], New York University [New York] (NYU), NYU System (NYU)-NYU System (NYU)-New York University [New York] (NYU), NYU System (NYU)-NYU System (NYU), Health for Development, Public Health England [Salisbury] (PHE), Kagoshima University, State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Research Centre in Infectious Diseases, CHUL Research Centre and Department of Microbiology and Immunology, Université Laval [Québec] (ULaval)-Faculty of Medicine, Institute of Plant Science and Resources, Okayama University, University of Guelph, Biologie Moléculaire du Gène chez les Extrêmophiles (BMGE), Institut Pasteur [Paris], US Geological Survey [Seattle], United States Geological Survey [Reston] (USGS), Northwestern University [Evanston], Centre International de Recherches Médicales de Franceville (CIRMF), Department of Pharmacology and Toxicology, University of Louisville, Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, Center for Infectious Disease, University of Texas at Austin [Austin], Novosibirsk State University (NSU), University of Veterinary Medicine [Vienna] (Vetmeduni), Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU), Texas Biomedical Research Institute [San Antonio, TX], Texas A&M University System, National Institute for Communicable Diseases [Johannesburg] (NICD), Queen's University [Belfast] (QUB), Instituto de Biotecnología y Biología Molecular [La Plata] (IBBM), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET)-Facultad de Ciencias Exactas [La Plata], Universidad Nacional de la Plata [Argentine] (UNLP)-Universidad Nacional de la Plata [Argentine] (UNLP), University of Freiburg [Freiburg], Department of Biochemistry, Molecular Biology, Entomology and Plant Pathology [Mstate, USA] (BCH-EPP), Mississippi State University [Mississippi], Summerland Research and Development Centre, Agriculture and Agri-Food [Ottawa] (AAFC), University of Maryland School of Medicine, University of Maryland System, Defence Science and Technology Laboratory (Dstl), Ministry of Defence (UK) (MOD), Department of Microbiology, Immunology and Pathology, Centre for Environment, Fisheries and Aquaculture Science [Weymouth] (CEFAS), Hokkaido University [Sapporo, Japan], Institute for Virus Research, Kyoto University [Kyoto], Stratégies antivirales, Institut Pasteur de Guinée, Réseau International des Instituts Pasteur (RIIP), Viral Special Pathogens Branch, Centers for Disease Control and Prevention-WHO Collaborative Centre for Viral Hemorrhagic Fevers, Bases moléculaires de la pathogénicité virale – Molecular Basis of Viral Pathogenicity (BMPV), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), National Biodefense Analysis and Countermeasures Center [Frederick], U.S. Social Security Administration, CSIRO Health & Biosecurity, Department of Agriculture, Fisheries and Forestry, Ecoscience Precinct, GPO Box 267, Brisbane, Duke-NUS Medical School [Singapore], Center for Fundamental and Applied Microbiomics, Arizona State University [Tempe] (ASU)-Biodesign Institute, Kansas State University, Departamento de Fitopatologia [Viçosa, Brazil] (BIOAGRO), Universidade Federal de Vicosa (UFV), This work was supported in part through Battelle Memorial Institute’s prime contract with the US National Institute of Allergy and Infectious Diseases (NIAID) under Contract No. HHSN272200700016I. A subcontractor to Battelle Memorial Institute who performed this work is J.H.K., an employee of Tunnell Government Services, Inc. This work was also funded in part under National Institutes of Health (NIH) contract HHSN272201000040I/HHSN27200004/D04 and R24AI120942 (N.V., R.B.T.), and the National Science Foundation (NSF) Individual Research and Development (IR/D) program (A.R.M.)., We thank Laura Bollinger (NIH/NIAID Integrated Research Facility at Fort Detrick, Frederick, MD, USA) for critically editing the manuscript, Andrew J. Davison (MRC – University of Glasgow Centre for Virus Research, Glasgow, UK) and Michael J. Adams (Department of Plant Pathology and Microbiology, Rothamsted Research, Harpenden, Herts, UK) of the ICTV Executive Committee for suggestions on manuscript improvement, and Arya Ariël Kuhn for sustained vocal support and (dia)critical remarks, Albert Einstein College of Medicine, Institut Hospitalier Universitaire Méditerranée Infection (IHU AMU), Queensland Alliance for Agriculture and Food Innovation, University of Queensland (UQ), Public Health England [Porton Down, Salisbury], Faculty of Medicine-Laval University [Québec], Okayama University [Okayama], Centre International de Recherches Médicales de Franceville, Texas Biomedical Research Institute [San Antonio, Texas], A&M University, National Institute for Communicable Diseases (NICD), Centre for Experimental Medicine [Queen’s University of Belfast], Department of Biochemistry, Molecular Biology, Entomology and Plant Pathology, Hokkaido University, Bases moléculaires de la pathogénicité virale – Molecular Basis of Viral Pathogenicity, Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Duke NUS Medical School, Departamento de Fitopatologia/BIOAGRO, Virology, U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Columbia University [New York], University of California [Irvine] (UC Irvine), University of California (UC), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM), The Scripps Research Institute [La Jolla, San Diego], University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), Philipps Universität Marburg = Philipps University of Marburg, University of Warwick [Coventry], Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Huazhong Agricultural University [Wuhan] (HZAU), Institut Pasteur [Paris] (IP), Agriculture and Agri-Food (AAFC), Kyoto University, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Universidade Federal de Viçosa = Federal University of Viçosa (UFV)
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0301 basic medicine ,MESH: Terminology as Topic ,media_common.quotation_subject ,Biología ,030106 microbiology ,Binomials ,Zoology ,Biology ,Points of View ,03 medical and health sciences ,Genus ,Terminology as Topic ,Genetics ,MESH: Classification ,Epithet ,Arenaviridae ,Ecology, Evolution, Behavior and Systematics ,Virus classification ,media_common ,Order Mononegavirales ,Evolutionary Biology ,Virus taxonomy ,Classification ,MESH: Viruses ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,Virus nomenclature ,Genealogy ,Ictv ,International committee on taxonomy of viruses ,030104 developmental biology ,Homo sapiens ,Viruses ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Mononegavirales - Abstract
Botanical, mycological, zoological, and prokaryotic species names follow the Linnaean format, consisting of an italicized Latinized binomen with a capitalized genus name and a lower case species epithet (e.g., Homo sapiens). Virus species names, however, do not follow a uniform format, and, even when binomial, are not Linnaean in style. In this thought exercise, we attempted toconvert all currently official names ofspecies included in the viru sfamily Arenaviridae and the virus order Mononegavirales to Linnaean binomials, and to identify and address associated challenges and concerns. Surprisingly, this endeavor was not as complicated or time-consuming as even the authors of this article expected when conceiving the experiment., La lista completa de autores que integran el documento puede consultarse en el archivo, Instituto de Biotecnologia y Biologia Molecular
17. Recombinant human thioredoxin ameliorates imiquimod-induced psoriasis-like dermatitis in mice.
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Mostafa A, Sakurai K, Murata T, Dainichi T, Tian H, Yodoi J, and Kabashima K
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Competing Interests: Conflict of Interest KK has received consulting fees or advisory board honoraria from Japan Tobacco Inc., Kao, LEO Pharma, Chugai Pharmaceutical, Maruho, Pola Pharma, Abbvie, Eli Lilly, Sanofi, and Pfizer, and has received research grants from LEO Pharma, Japan Tobacco Inc., P&G Japan, Eli Lilly Japan, Mitsubishi Tanabe, Ono Pharmaceutical, Kyowa Kirin, Pola Pharma, AbbVie, Sanofi, KOSÉ, and Kyorin Pharmaceutical. TD has received scholarship donations and/or lecture fees from AbbVie, Eli Lilly, Janssen, Kyowa Kirin, Maruho, Otsuka, Pfizer, Taiho Pharmaceutical, Torii Pharmaceutical, Sanofi, and Sun Pharma, and fees for members of the Clinical Trial Review Committee from Teikoku Parmaceutical, and research advisory fees from Yushin Brewer, and research grants from Hoyu, KOSÉ, Maruho, and Terumo.
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- 2024
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18. Human cytomegalovirus harnesses host L1 retrotransposon for efficient replication.
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Hwang SY, Kim H, Denisko D, Zhao B, Lee D, Jeong J, Kim J, Park K, Park J, Jeong D, Park S, Choi HJ, Kim S, Lee EA, and Ahn K
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- Humans, Cytomegalovirus Infections virology, Cytomegalovirus Infections genetics, Host-Pathogen Interactions genetics, Retroelements genetics, DNA-Binding Proteins, Cytomegalovirus genetics, Cytomegalovirus physiology, Virus Replication genetics, Viral Proteins metabolism, Viral Proteins genetics, DNA Replication genetics, Long Interspersed Nucleotide Elements genetics
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Genetic parasites, including viruses and transposons, exploit components from the host for their own replication. However, little is known about virus-transposon interactions within host cells. Here, we discover a strategy where human cytomegalovirus (HCMV) hijacks L1 retrotransposon encoded protein during its replication cycle. HCMV infection upregulates L1 expression by enhancing both the expression of L1-activating transcription factors, YY1 and RUNX3, and the chromatin accessibility of L1 promoter regions. Increased L1 expression, in turn, promotes HCMV replicative fitness. Affinity proteomics reveals UL44, HCMV DNA polymerase subunit, as the most abundant viral binding protein of the L1 ribonucleoprotein (RNP) complex. UL44 directly interacts with L1 ORF2p, inducing DNA damage responses in replicating HCMV compartments. While increased L1-induced mutagenesis is not observed in HCMV for genetic adaptation, the interplay between UL44 and ORF2p accelerates viral DNA replication by alleviating replication stress. Our findings shed light on how HCMV exploits host retrotransposons for enhanced viral fitness., (© 2024. The Author(s).)
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- 2024
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19. Redoxisome Update: TRX and TXNIP/TBP2-Dependent Regulation of NLRP-1/NLRP-3 Inflammasome.
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Yoshihara E, Matsuo Y, Masaki S, Chen Z, Tian H, Masutani H, Yamauchi A, Hirota K, and Yodoi J
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- Oxidation-Reduction, Thioredoxins metabolism, Inflammasomes metabolism, NLR Family, Pyrin Domain-Containing 3 Protein metabolism
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Recent studies have provided evidence for the direct binding of thioredoxin-1 (TRX1) to a component of inflammasome complex NLR family pyrin domain containing 1 (NLRP-1). This interaction suggests a potential role for TRX1 in the regulation of the NLRP-1 inflammasome. Furthermore, the NLRP-3 inflammasome is known to bind TRX1 and its inhibitor, TRX-binding protein-2/TRX-interacting protein/vitamin D3 upregulated protein-1 (TBP2/TXNIP/VDUP-1). This binding forms a redox-sensitive complex, termed the "Redoxisome," as described previously. However, the specific functions of NLRP-1 within the redoxisome complex remain undefined. Antioxid. Redox Signal. 40, 595-597.
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- 2024
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20. Enterovirus A71 does not meet the uncoating receptor SCARB2 at the cell surface.
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Nishimura Y, Sato K, Koyanagi Y, Wakita T, Muramatsu M, Shimizu H, Bergelson JM, and Arita M
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- Humans, Cell Membrane metabolism, Cell Line, Receptors, Scavenger genetics, Receptors, Scavenger metabolism, Lysosomal Membrane Proteins genetics, Enterovirus metabolism, Enterovirus A, Human genetics, Enterovirus A, Human metabolism, Enterovirus Infections
- Abstract
Enterovirus A71 (EV-A71) infection involves a variety of receptors. Among them, two transmembrane protein receptors have been investigated in detail and shown to be critical for infection: P-selectin glycoprotein ligand-1 (PSGL-1) in lymphocytes (Jurkat cells), and scavenger receptor class B member 2 (SCARB2) in rhabdomyosarcoma (RD) cells. PSGL-1 and SCARB2 have been reported to be expressed on the surface of Jurkat and RD cells, respectively. In the work reported here, we investigated the roles of PSGL-1 and SCARB2 in the process of EV-A71 entry. We first examined the expression of SCARB2 in Jurkat cells, and detected it within the cytoplasm, but not on the cell surface. Further, using PSGL-1 and SCARB2 knockout cells, we found that although both PSGL-1 and SCARB2 are essential for virus infection of Jurkat cells, virus attachment to these cells requires only PSGL-1. These results led us to evaluate the cell surface expression and the roles of SCARB2 in other EV-A71-susceptible cell lines. Surprisingly, in contrast to the results of previous studies, we found that SCARB2 is absent from the surface of RD cells and other susceptible cell lines we examined, and that although SCARB2 is essential for infection of these cells, it is dispensable for virus attachment. These results indicate that a receptor other than SCARB2 is responsible for virus attachment to the cell and probably for internalization of virions, not only in Jurkat cells but also in RD cells and other EV-A71-susceptible cells. SCARB2 is highly concentrated in lysosomes and late endosomes, where it is likely to trigger acid-dependent uncoating of virions, the critical final step of the entry process. Our results suggest that the essential interactions between EV-A71 and SCARB2 occur, not at the cell surface, but within the cell., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Nishimura et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2024
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21. Geranylgeranylacetone Ameliorates Skin Inflammation by Regulating and Inducing Thioredoxin via the Thioredoxin Redox System.
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Jin T, You Y, Fan W, Wang J, Chen Y, Li S, Hong S, Wang Y, Cao R, Yodoi J, and Tian H
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Geranylgeranylacetone (GGA) exerts cytoprotective activity against various toxic stressors via the thioredoxin (TRX) redox system; however, its effect on skin inflammation and molecular mechanism on inducing the TRX of GGA is still unknown. We investigated the effects of GGA in a murine irritant contact dermatitis (ICD) model induced by croton oil. Both a topical application and oral administration of GGA induced TRX production and Nrf2 activation. GGA ameliorated ear swelling, neutrophil infiltration, and inhibited the expression of TNF-α, IL-1β, GM-CSF, and 8-OHdG. GGA's cytoprotective effect was stronger orally than topically in mice. In vitro studies also showed that GGA suppressed the expression of NLRP3, TNF-α, IL-1β, and GM-CSF and scavenged ROS in PAM212 cells after phorbol myristate acetate stimulation. Moreover, GGA induced endogenous TRX production and Nrf2 nuclear translocation in PAM212 cells (dependent on the presence of ROS) and activated the PI3K-Akt signaling pathway. GGA significantly downregulated thioredoxin-interacting protein (TXNIP) levels in PAM212 cells treated with or without Nrf2 siRNA. After knocking down Nrf2 in PAM212 cells, the effect of GGA on TRX induction was significantly inhibited. This suggests that GGA suppress ICD by inducing endogenous TRX, which may be regulated by PI3K/Akt/Nrf2 mediation of the TRX redox system.
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- 2023
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22. Prospect of thioredoxin as a possibly effective tool to combat OSAHS.
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Pan Y, Lu Y, Zhou JD, Wang CX, Wang JQ, Fukunaga A, Yodoi J, and Tian H
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- Humans, Reactive Oxygen Species metabolism, Antioxidants, Cytokines, Inflammation, Thioredoxins, Sleep Apnea, Obstructive therapy, Sleep Apnea, Obstructive metabolism
- Abstract
Purpose: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is characterized by recurrent upper airway disturbances during sleep leading to episodes of hypopnea or apnea, followed by hypoxemia and subsequent reoxygenation. It is believed that this reoxygenation/reperfusion stage leads to oxidative stress, which then leads to inflammation and cardiovascular diseases. The treatments of patient with OSAHS include surgical and non-surgical therapies with various side effects and common complaints. Therefore, it is important to develop a new, safe, and effective therapeutic treatment. As a small-molecule multifunctional protein, thioredoxin (TRX) has antioxidant and redox regulatory functions at the active site Cys-Gly-Pro. TRX prevents inflammation by suppressing the production of pro-inflammatory cytokines rather than suppressing the immune response., Methods: We review the papers on the pathophysiological process of OSAHS and the antioxidative and anti-inflammatory effects of TRX., Results: TRX may play a role in OSAHS by scavenging ROS, blocking the production of inflammatory cytokines, inhibiting the migration and activation of neutrophils, and controlling the activation of ROS-dependent inflammatory signals by regulating the redox state of intracellular target particles. Furthermore, TRX regulates the synthesis, stability, and activity of hypoxia-inducible factor 1 (HIF-1). TRX also has an inhibitory effect on endoplasmic reticulum- and mitochondria-induced apoptosis by regulating the expression of BAX, BCL2, p53, and ASK1., Conclusion: Understanding the function of TRX may be useful for the treatment of OSAHS., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
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- 2023
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23. The chromatin remodeler RSC prevents ectopic CENP-A propagation into pericentromeric heterochromatin at the chromatin boundary.
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Tsunemine S, Nakagawa H, Suzuki Y, and Murakami Y
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- Heterochromatin metabolism, Chromatin metabolism, Centromere Protein A metabolism, Chromosomal Proteins, Non-Histone genetics, Chromosomal Proteins, Non-Histone metabolism, Centromere metabolism, Kinetochores metabolism, Histones metabolism, Schizosaccharomyces genetics, Schizosaccharomyces metabolism, Schizosaccharomyces pombe Proteins genetics, Schizosaccharomyces pombe Proteins metabolism
- Abstract
Centromeres of most eukaryotes consist of two distinct chromatin domains: a kinetochore domain, identified by the histone H3 variant, CENP-A, and a heterochromatic domain. How these two domains are separated is unclear. Here, we show that, in Schizosaccharomyces pombe, mutation of the chromatin remodeler RSC induced CENP-ACnp1 misloading at pericentromeric heterochromatin, resulting in the mis-assembly of kinetochore proteins and a defect in chromosome segregation. We find that RSC functions at the kinetochore boundary to prevent CENP-ACnp1 from spreading into neighbouring heterochromatin, where deacetylated histones provide an ideal environment for the spread of CENP-ACnp1. In addition, we show that RSC decompacts the chromatin structure at this boundary, and propose that this RSC-directed chromatin decompaction prevents mis-propagation of CENP-ACnp1 into pericentromeric heterochromatin. Our study provides an insight into how the distribution of distinct chromatin domains is established and maintained., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)
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- 2022
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24. Correction: PKR and TLR3 trigger distinct signals that coordinate the induction of antiviral apoptosis.
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Zuo W, Wakimoto M, Kozaiwa N, Shirasaka Y, Oh SW, Fujiwara S, Miyachi H, Kogure A, Kato H, and Fujita T
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- 2022
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25. PKR and TLR3 trigger distinct signals that coordinate the induction of antiviral apoptosis.
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Zuo W, Wakimoto M, Kozaiwa N, Shirasaka Y, Oh SW, Fujiwara S, Miyachi H, Kogure A, Kato H, and Fujita T
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- Apoptosis, Interferon-beta genetics, RNA, Double-Stranded genetics, RNA, Viral metabolism, eIF-2 Kinase genetics, eIF-2 Kinase metabolism, Antiviral Agents pharmacology, Toll-Like Receptor 3 genetics, Toll-Like Receptor 3 metabolism
- Abstract
RIG-I-like receptors (RLRs), protein kinase R (PKR), and endosomal Toll-like receptor 3 (TLR3) sense viral non-self RNA and are involved in cell fate determination. However, the mechanisms by which intracellular RNA induces apoptosis, particularly the role of each RNA sensor, remain unclear. We performed cytoplasmic injections of different types of RNA and elucidated the molecular mechanisms underlying viral dsRNA-induced apoptosis. The results obtained revealed that short 5'-triphosphate dsRNA, the sole ligand of RIG-I, induced slow apoptosis in a fraction of cells depending on IRF-3 transcriptional activity and IFN-I production. However, intracellular long dsRNA was sensed by PKR and TLR3, which activate distinct signals, and synergistically induced rapid apoptosis. PKR essentially induced translational arrest, resulting in reduced levels of cellular FLICE-like inhibitory protein and functioned in the TLR3/TRIF-dependent activation of caspase 8. The present results demonstrated that PKR and TLR3 were both essential for inducing the viral RNA-mediated apoptosis of infected cells and the arrest of viral production., (© 2022. The Author(s).)
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- 2022
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26. Mutations equivalent to Drosophila mago nashi mutants imply reduction of Magoh protein incorporation into exon junction complex.
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Oshizuki S, Matsumoto E, Tanaka S, and Kataoka N
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- Animals, Exons genetics, Mutation, RNA Splicing genetics, RNA, Messenger genetics, RNA, Messenger metabolism, Drosophila genetics, Nuclear Proteins metabolism
- Abstract
Pre-mRNA splicing imprints mRNAs by depositing multi-protein complexes, termed exon junction complexes (EJCs). The EJC core consists of four proteins, eIF4AIII, MLN51, Y14 and Magoh. Magoh is a human homolog of Drosophila mago nashi protein, which is involved in oskar mRNA localization in Drosophila oocytes. Here we determined the effects of Magoh mutations equivalent to those of Drosophila mago nashi mutant proteins that cause mis-localization of oskar mRNA. We found that Magoh I90T mutation caused mis-localization of Magoh protein in the cytoplasm by reducing its binding activity to Y14. On the other hand, G18R mutation did not affect its binding to Y14, but this mutation reduced its association with spliced mRNAs. Our results strongly suggest that Magoh mutations equivalent to Drosophila mago nashi mutants cause improper EJC formation by reducing incorporation of Magoh into EJC., (© 2022 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.)
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- 2022
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27. Urinary Thioredoxin as a Biomarker of Renal Redox Dysregulation and a Companion Diagnostic to Identify Responders to Redox-Modulating Therapeutics.
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Kasuno K, Yodoi J, and Iwano M
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- Biomarkers urine, Female, Humans, Male, Oleanolic Acid analogs & derivatives, Oxidation-Reduction, Thioredoxins, Acute Kidney Injury diagnosis, Acute Kidney Injury drug therapy, Acute Kidney Injury etiology, Renal Insufficiency, Chronic diagnosis, Renal Insufficiency, Chronic drug therapy, Renal Insufficiency, Chronic etiology
- Abstract
Significance: The development and progression of renal diseases, including acute kidney injury (AKI) and chronic kidney disease (CKD), are the result of heterogeneous pathophysiology that reflects a range of environmental factors and, in a lesser extent, genetic mutations. The pathophysiology specific to most kidney diseases is not currently identified; therefore, these diseases are diagnosed based on non-pathological factors. For that reason, pathophysiology-based companion diagnostics for selection of pathophysiology-targeted treatments have not been available, which impedes personalized medicine in kidney disease. Recent Advances: Pathophysiology-targeted therapeutic agents are now being developed for the treatment of redox dysregulation. Redox modulation therapeutics, including bardoxolone methyl, suppresses the onset and progression of AKI and CKD. On the other hand, pathophysiology-targeted diagnostics for renal redox dysregulation are also being developed. Urinary thioredoxin (TXN) is a biomarker that can be used to diagnose tubular redox dysregulation. AKI causes oxidation and urinary excretion of TXN, which depletes TXN from the tubules, resulting in tubular redox dysregulation. Urinary TXN is selectively elevated at the onset of AKI and correlates with the progression of CKD in diabetic nephropathy. Critical Issues: Diagnostic methods should provide information about molecular mechanisms that aid in the selection of appropriate therapies to improve the prognosis of kidney disease. Future Directions: A specific diagnostic method enabling detection of redox dysregulation based on pathological molecular mechanisms is much needed and could provide the first step toward personalized medicine in kidney disease. Urinary TXN is a candidate for a companion diagnostic method to identify responders to redox-modulating therapeutics. Antioxid. Redox Signal. 36, 1051-1065.
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- 2022
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28. Thioredoxin-1: A Promising Target for the Treatment of Allergic Diseases.
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Wang J, Zhou J, Wang C, Fukunaga A, Li S, Yodoi J, and Tian H
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- Animals, Inflammation drug therapy, Oxidation-Reduction, Thioredoxins metabolism, Asthma drug therapy, Rhinitis, Allergic
- Abstract
Thioredoxin-1 (Trx1) is an important regulator of cellular redox homeostasis that comprises a redox-active dithiol. Trx1 is induced in response to various stress conditions, such as oxidative damage, infection or inflammation, metabolic dysfunction, irradiation, and chemical exposure. It has shown excellent anti-inflammatory and immunomodulatory effects in the treatment of various human inflammatory disorders in animal models. This review focused on the protective roles and mechanisms of Trx1 in allergic diseases, such as allergic asthma, contact dermatitis, food allergies, allergic rhinitis, and drug allergies. Trx1 plays an important role in allergic diseases through processes, such as antioxidation, inhibiting macrophage migration inhibitory factor (MIF), regulating Th1/Th2 immune balance, modulating allergic inflammatory cells, and suppressing complement activation. The regulatory mechanism of Trx1 differs from that of glucocorticoids that regulates the inflammatory reactions associated with immune response suppression. Furthermore, Trx1 exerts a beneficial effect on glucocorticoid resistance of allergic inflammation by inhibiting the production and internalization of MIF. Our results suggest that Trx1 has the potential for future success in translational research., Competing Interests: Author HT was employed by Jiaozhimei Biotechnology (Shaoxing) Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Zhou, Wang, Fukunaga, Li, Yodoi and Tian.)
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- 2022
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29. BDNF controls GABA A R trafficking and related cognitive processes via autophagic regulation of p62.
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Tomoda T, Sumitomo A, Shukla R, Hirota-Tsuyada Y, Miyachi H, Oh H, French L, and Sibille E
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- Animals, Autophagy, Cognition, Mice, Receptors, GABA-A, Sequestosome-1 Protein, Synaptic Transmission, Brain-Derived Neurotrophic Factor metabolism, gamma-Aminobutyric Acid
- Abstract
Reduced brain-derived neurotrophic factor (BDNF) and gamma-aminobutyric acid (GABA) neurotransmission co-occur in brain conditions (depression, schizophrenia and age-related disorders) and are associated with symptomatology. Rodent studies show they are causally linked, suggesting the presence of biological pathways mediating this link. Here we first show that reduced BDNF and GABA also co-occur with attenuated autophagy in human depression. Using mice, we then show that reducing Bdnf levels (Bdnf
+/- ) leads to upregulated sequestosome-1/p62, a key autophagy-associated adaptor protein, whose levels are inversely correlated with autophagic activity. Reduced Bdnf levels also caused reduced surface presentation of α5 subunit-containing GABAA receptor (α5-GABAA R) in prefrontal cortex (PFC) pyramidal neurons. Reducing p62 gene dosage restored α5-GABAA R surface expression and rescued PFC-relevant behavioral deficits of Bdnf+/- mice, including cognitive inflexibility and reduced sensorimotor gating. Increasing p62 levels was sufficient to recreate the molecular and behavioral profiles of Bdnf+/- mice. Collectively, the data reveal a novel mechanism by which deficient BDNF leads to targeted reduced GABAergic signaling through autophagic dysregulation of p62, potentially underlying cognitive impairment across brain conditions., (© 2021. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)- Published
- 2022
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30. Virus-infection in cochlear supporting cells induces audiosensory receptor hair cell death by TRAIL-induced necroptosis.
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Hayashi Y, Suzuki H, Nakajima W, Uehara I, Tanimura A, Himeda T, Koike S, Katsuno T, Kitajiri SI, Koyanagi N, Kawaguchi Y, Onomoto K, Kato H, Yoneyama M, Fujita T, and Tanaka N
- Subjects
- Animals, Cells, Cultured, Hair Cells, Auditory immunology, Hair Cells, Auditory pathology, Hearing Loss, Sensorineural immunology, Hearing Loss, Sensorineural pathology, Mice, Inbred ICR, Virus Diseases immunology, Virus Diseases pathology, Mice, Hair Cells, Auditory virology, Hearing Loss, Sensorineural virology, Necroptosis, TNF-Related Apoptosis-Inducing Ligand immunology, Virus Diseases complications
- Abstract
Although sensorineural hearing loss (SHL) is relatively common, its cause has not been identified in most cases. Previous studies have suggested that viral infection is a major cause of SHL, especially sudden SHL, but the system that protects against pathogens in the inner ear, which is isolated by the blood-labyrinthine barrier, remains poorly understood. We recently showed that, as audiosensory receptor cells, cochlear hair cells (HCs) are protected by surrounding accessory supporting cells (SCs) and greater epithelial ridge (GER or Kölliker's organ) cells (GERCs) against viral infections. Here, we found that virus-infected SCs and GERCs induce HC death via production of the tumour necrosis factor-related apoptosis-inducing ligand (TRAIL). Notably, the HCs expressed the TRAIL death receptors (DR) DR4 and DR5, and virus-induced HC death was suppressed by TRAIL-neutralizing antibodies. TRAIL-induced HC death was not caused by apoptosis, and was inhibited by necroptosis inhibitors. Moreover, corticosteroids, the only effective drug for SHL, inhibited the virus-induced transformation of SCs and GERCs into macrophage-like cells and HC death, while macrophage depletion also inhibited virus-induced HC death. These results reveal a novel mechanism underlying virus-induced HC death in the cochlear sensory epithelium and suggest a possible target for preventing virus-induced SHL., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2021
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31. Redox Regulation in Aging Lungs and Therapeutic Implications of Antioxidants in COPD.
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Kiyokawa H, Hoshino Y, Sakaguchi K, Muro S, and Yodoi J
- Abstract
Mammals, including humans, are aerobic organisms with a mature respiratory system to intake oxygen as a vital source of cellular energy. Despite the essentiality of reactive oxygen species (ROS) as byproducts of aerobic metabolism for cellular homeostasis, excessive ROS contribute to the development of a wide spectrum of pathological conditions, including chronic lung diseases such as COPD. In particular, epithelial cells in the respiratory system are directly exposed to and challenged by exogenous ROS, including ozone and cigarette smoke, which results in detrimental oxidative stress in the lungs. In addition, the dysfunction of redox regulation due to cellular aging accelerates COPD pathogenesis, such as inflammation, protease anti-protease imbalance and cellular apoptosis. Therefore, various drugs targeting oxidative stress-associated pathways, such as thioredoxin and N-acetylcysteine, have been developed for COPD treatment to precisely regulate the redox system. In this review, we present the current understanding of the roles of redox regulation in the respiratory system and COPD pathogenesis. We address the insufficiency of current COPD treatment as antioxidants and discuss future directions in COPD therapeutics targeting oxidative stress while avoiding side effects such as tumorigenesis.
- Published
- 2021
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32. Effect of chronic administration with human thioredoxin-1 transplastomic lettuce on diabetic mice.
- Author
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Watanabe R, Ashida H, Kobayashi-Miura M, Yokota A, and Yodoi J
- Abstract
Scope: Human thioredoxin-1 (hTrx-1) is a defensive protein induced by various stresses and exerts antioxidative and anti-inflammatory effects. Previously, we described a transplastomic lettuce overexpressing hTrx-1 that exerts a protective effect against oxidative damage in a pancreatic β-cell line. In this study, we treated diabetic mice (Akita mice) with exogenous hTrx-1 and evaluated the effects., Methods and Results: Treatment with drinking water and single applications of exogenous hTrx-1 did not influence the feeding, drinking behavior, body weight, blood glucose, or glycosylated hemoglobin (HbA
1c ) levels in Akita mice. However, chronic administration of a 10% hTrx-1 lettuce-containing diet was associated with a significant reduction from the baseline of HbA1c levels compared with mice fed a wild-type lettuce-containing diet. It also resulted in an increased number of goblet cells in the small intestine, indicating that mucus was synthesized and secreted., Conclusion: Our results revealed that the administration of an hTrx-1 lettuce-containing diet improves the baseline level of HbA1c in Akita mice. This effect is mediated through goblet cell proliferation and possibly related to protection against postprandial hyperglycemia by mucus, which results in the improvement of blood glucose control. These findings suggest that the hTrx-1 lettuce may be a useful tool for the continuous antioxidative and antidiabetic efficacies of the hTrx-1 protein., Competing Interests: The authors have declared no conflicts of interest., (© 2021 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)- Published
- 2021
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33. TREM2 is a receptor for non-glycosylated mycolic acids of mycobacteria that limits anti-mycobacterial macrophage activation.
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Iizasa E, Chuma Y, Uematsu T, Kubota M, Kawaguchi H, Umemura M, Toyonaga K, Kiyohara H, Yano I, Colonna M, Sugita M, Matsuzaki G, Yamasaki S, Yoshida H, and Hara H
- Subjects
- Adaptor Proteins, Signal Transducing genetics, Adaptor Proteins, Signal Transducing metabolism, Animals, CARD Signaling Adaptor Proteins genetics, CARD Signaling Adaptor Proteins metabolism, Cell Wall metabolism, Cells, Cultured, Disease Models, Animal, Female, Glycolipids metabolism, Humans, Latent Tuberculosis microbiology, Lectins, C-Type genetics, Lectins, C-Type metabolism, Macrophage Activation immunology, Macrophages immunology, Male, Membrane Glycoproteins genetics, Membrane Proteins genetics, Membrane Proteins metabolism, Mice, Mice, Knockout, Mycobacterium tuberculosis metabolism, Mycobacterium tuberculosis pathogenicity, Primary Cell Culture, Receptors, IgG metabolism, Receptors, Immunologic genetics, Virulence Factors metabolism, Immune Evasion, Latent Tuberculosis immunology, Membrane Glycoproteins metabolism, Mycobacterium tuberculosis immunology, Mycolic Acids metabolism, Receptors, Immunologic metabolism
- Abstract
Mycobacterial cell-wall glycolipids elicit an anti-mycobacterial immune response via FcRγ-associated C-type lectin receptors, including Mincle, and caspase-recruitment domain family member 9 (CARD9). Additionally, mycobacteria harbor immuno-evasive cell-wall lipids associated with virulence and latency; however, a mechanism of action is unclear. Here, we show that the DAP12-associated triggering receptor expressed on myeloid cells 2 (TREM2) recognizes mycobacterial cell-wall mycolic acid (MA)-containing lipids and suggest a mechanism by which mycobacteria control host immunity via TREM2. Macrophages respond to glycosylated MA-containing lipids in a Mincle/FcRγ/CARD9-dependent manner to produce inflammatory cytokines and recruit inducible nitric oxide synthase (iNOS)-positive mycobactericidal macrophages. Conversely, macrophages respond to non-glycosylated MAs in a TREM2/DAP12-dependent but CARD9-independent manner to recruit iNOS-negative mycobacterium-permissive macrophages. Furthermore, TREM2 deletion enhances Mincle-induced macrophage activation in vitro and inflammation in vivo and accelerates the elimination of mycobacterial infection, suggesting that TREM2-DAP12 signaling counteracts Mincle-FcRγ-CARD9-mediated anti-mycobacterial immunity. Mycobacteria, therefore, harness TREM2 for immune evasion.
- Published
- 2021
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34. Genome wide association study of HTLV-1-associated myelopathy/tropical spastic paraparesis in the Japanese population.
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Penova M, Kawaguchi S, Yasunaga JI, Kawaguchi T, Sato T, Takahashi M, Shimizu M, Saito M, Tsukasaki K, Nakagawa M, Takenouchi N, Hara H, Matsuura E, Nozuma S, Takashima H, Izumo S, Watanabe T, Uchimaru K, Iwanaga M, Utsunomiya A, Tabara Y, Paul R, Yamano Y, Matsuoka M, and Matsuda F
- Subjects
- Chromosome Mapping, Human T-lymphotropic virus 1 isolation & purification, Humans, Japan, Polymorphism, Single Nucleotide, Viral Load, Genome-Wide Association Study, HLA Antigens genetics, Human T-lymphotropic virus 1 pathogenicity, Paraparesis, Tropical Spastic genetics
- Abstract
HTLV-1-associated myelopathy (HAM/TSP) is a chronic and progressive inflammatory disease of the central nervous system. The aim of our study was to identify genetic determinants related to the onset of HAM/TSP in the Japanese population. We conducted a genome-wide association study comprising 753 HAM/TSP patients and 899 asymptomatic HTLV-1 carriers. We also performed comprehensive genotyping of HLA-A , -B , -C , -DPB1 , -DQB1 , and -DRB1 genes using next-generation sequencing technology for 651 HAM/TSP patients and 804 carriers. A strong association was observed in HLA class I ( P = 1.54 × 10
-9 ) and class II ( P = 1.21 × 10-8 ) loci with HAM/TSP. Association analysis using HLA genotyping results showed that HLA-C * 07:02 ( P = 2.61 × 10-5 ), HLA-B * 07:02 ( P = 4.97 × 10-10 ), HLA-DRB1 * 01:01 ( P = 1.15 × 10-9 ) and HLA-DQB1 * 05:01 ( P = 2.30 × 10-9 ) were associated with disease risk, while HLA-B * 40:06 ( P = 3.03 × 10-5 ), HLA-DRB1 * 15:01 ( P = 1.06 × 10-5 ) and HLA-DQB1 * 06:02 ( P = 1.78 × 10-6 ) worked protectively. Logistic regression analysis identified amino acid position 7 in the G-BETA domain of HLA-DRB1 as strongly associated with HAM/TSP ( P = 9.52 × 10-10 ); individuals homozygous for leucine had an associated increased risk of HAM/TSP (odds ratio, 9.57), and proline was protective (odds ratio, 0.65). Both associations were independent of the known risk associated with proviral load. DRB1-GB-7-Leu was not significantly associated with proviral load. We have identified DRB1-GB-7-Leu as a genetic risk factor for HAM/TSP development independent of proviral load. This suggests that the amino acid residue may serve as a specific marker to identify the risk of HAM/TSP even without knowledge of proviral load. In light of its allele frequency worldwide, this biomarker will likely prove useful in HTLV-1 endemic areas across the globe., Competing Interests: Competing interest statement: S.K. and F.M. are board members of GenoConcierge Kyoto Inc. S.K., M. Shimizu, and F.M. have patents pending for HLA typing software, primer sets for PCR amplification of HLA genes and its experimental protocol, and a risk marker of DRB1-GB-7 for HAM/TSP development., (Copyright © 2021 the Author(s). Published by PNAS.)- Published
- 2021
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35. NOD 2 Mutation-Associated Case with Blau Syndrome Triggered by BCG Vaccination.
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Arakawa A, Kambe N, Nishikomori R, Tanabe A, Ueda M, Nishigori C, Miyachi Y, and Kanazawa N
- Abstract
We describe a patient who developed multiple granulomatous skin lesions after Bacille de Calmette et Guérin (BCG) vaccination without significant effect by topical corticosteroid, followed by painless cystic tumors on the bilateral knees and hands and inflammatory changes on ophthalmologic examination. A functional mutation in NOD 2 was detected by a genetic analysis, and he was diagnosed as sporadic Blau syndrome. Since NOD 2 acts as a sensor for the BCG component, it is possible that BCG vaccination may trigger granuloma formation in Blau syndrome patients with such genetic background.
- Published
- 2021
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36. Progress in the mechanism and targeted drug therapy for COPD.
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Wang C, Zhou J, Wang J, Li S, Fukunaga A, Yodoi J, and Tian H
- Subjects
- Cyclic AMP-Dependent Protein Kinases metabolism, Cytokines metabolism, Humans, Oxidation-Reduction drug effects, Phosphatidylinositol 3-Kinases metabolism, Proto-Oncogene Proteins c-akt metabolism, Drug Delivery Systems, MAP Kinase Signaling System drug effects, Pulmonary Disease, Chronic Obstructive drug therapy, Pulmonary Disease, Chronic Obstructive metabolism, Thioredoxins metabolism
- Abstract
Chronic obstructive pulmonary disease (COPD) is emphysema and/or chronic bronchitis characterised by long-term breathing problems and poor airflow. The prevalence of COPD has increased over the last decade and the drugs most commonly used to treat it, such as glucocorticoids and bronchodilators, have significant therapeutic effects; however, they also cause side effects, including infection and immunosuppression. Here we reviewed the pathogenesis and progression of COPD and elaborated on the effects and mechanisms of newly developed molecular targeted COPD therapeutic drugs. Among these new drugs, we focussed on thioredoxin (Trx). Trx effectively prevents the progression of COPD by regulating redox status and protease/anti-protease balance, blocking the NF-κB and MAPK signalling pathways, suppressing the activation and migration of inflammatory cells and the production of cytokines, inhibiting the synthesis and the activation of adhesion factors and growth factors, and controlling the cAMP-PKA and PI3K/Akt signalling pathways. The mechanism by which Trx affects COPD is different from glucocorticoid-based mechanisms which regulate the inflammatory reaction in association with suppressing immune responses. In addition, Trx also improves the insensitivity of COPD to steroids by inhibiting the production and internalisation of macrophage migration inhibitory factor (MIF). Taken together, these findings suggest that Trx may be the ideal drug for treating COPD.
- Published
- 2020
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37. H3K9 Demethylases JMJD1A and JMJD1B Control Prospermatogonia to Spermatogonia Transition in Mouse Germline.
- Author
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Kuroki S, Maeda R, Yano M, Kitano S, Miyachi H, Fukuda M, Shinkai Y, and Tachibana M
- Subjects
- Animals, Biocatalysis, Chromosomes, Mammalian genetics, Demethylation, Gene Expression Profiling, Isoenzymes metabolism, Jumonji Domain-Containing Histone Demethylases genetics, Male, Mice, Models, Biological, Transcription, Genetic, Germ Cells cytology, Jumonji Domain-Containing Histone Demethylases metabolism, Spermatogonia cytology
- Abstract
Histone H3 lysine 9 (H3K9) methylation is dynamically regulated by methyltransferases and demethylases. In spermatogenesis, prospermatogonia differentiate into differentiating or undifferentiated spermatogonia after birth. However, the epigenetic regulation of prospermatogonia to spermatogonia transition is largely unknown. We found that perinatal prospermatogonia have extremely low levels of di-methylated H3K9 (H3K9me2) and that H3K9 demethylases, JMJD1A and JMJD1B, catalyze H3K9me2 demethylation in perinatal prospermatogonia. Depletion of JMJD1A and JMJD1B in the embryonic germline resulted in complete loss of male germ cells after puberty, indicating that H3K9me2 demethylation is essential for male germline maintenance. JMJD1A/JMJD1B-depleted germ cells were unable to differentiate into functional spermatogonia. JMJD1 isozymes contributed to activation of several spermatogonial stem cell maintenance genes through H3K9 demethylation during the prospermatogonia to spermatogonia transition, which we propose is key for spermatogonia development. In summary, JMJD1A/JMJD1B-mediated H3K9me2 demethylation promotes prospermatogonia to differentiate into functional spermatogonia by establishing proper gene expression profiles., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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38. Thioredoxin-1 maintains mitochondrial function via mechanistic target of rapamycin signalling in the heart.
- Author
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Oka SI, Chin A, Park JY, Ikeda S, Mizushima W, Ralda G, Zhai P, Tong M, Byun J, Tang F, Einaga Y, Huang CY, Kashihara T, Zhao M, Nah J, Tian B, Hirabayashi Y, Yodoi J, and Sadoshima J
- Subjects
- Animals, Cells, Cultured, Disease Models, Animal, Gene Expression Regulation, Heart Failure genetics, Heart Failure pathology, Heart Failure physiopathology, Mice, Inbred C57BL, Mice, Knockout, Mitochondria, Heart pathology, Myocytes, Cardiac pathology, Oxidative Stress, Rats, Wistar, Signal Transduction, Thioredoxins genetics, Energy Metabolism genetics, Heart Failure metabolism, Mitochondria, Heart metabolism, Myocytes, Cardiac metabolism, TOR Serine-Threonine Kinases metabolism, Thioredoxins metabolism
- Abstract
Aims: Thioredoxin 1 (Trx1) is an evolutionarily conserved oxidoreductase that cleaves disulphide bonds in oxidized substrate proteins such as mechanistic target of rapamycin (mTOR) and maintains nuclear-encoded mitochondrial gene expression. The cardioprotective effect of Trx1 has been demonstrated via cardiac-specific overexpression of Trx1 and dominant negative Trx1. However, the pathophysiological role of endogenous Trx1 has not been defined with a loss-of-function model. To address this, we have generated cardiac-specific Trx1 knockout (Trx1cKO) mice., Methods and Results: Trx1cKO mice were viable but died with a median survival age of 25.5 days. They developed heart failure, evidenced by contractile dysfunction, hypertrophy, and increased fibrosis and apoptotic cell death. Multiple markers consistently indicated increased oxidative stress and RNA-sequencing revealed downregulation of genes involved in energy production in Trx1cKO mice. Mitochondrial morphological abnormality was evident in these mice. Although heterozygous Trx1cKO mice did not show any significant baseline phenotype, pressure-overload-induced cardiac dysfunction, and downregulation of metabolic genes were exacerbated in these mice. mTOR was more oxidized and phosphorylation of mTOR substrates such as S6K and 4EBP1 was impaired in Trx1cKO mice. In cultured cardiomyocytes, Trx1 knockdown inhibited mitochondrial respiration and metabolic gene promoter activity, suggesting that Trx1 maintains mitochondrial function in a cell autonomous manner. Importantly, mTOR-C1483F, an oxidation-resistant mutation, prevented Trx1 knockdown-induced mTOR oxidation and inhibition and attenuated suppression of metabolic gene promoter activity., Conclusion: Endogenous Trx1 is essential for maintaining cardiac function and metabolism, partly through mTOR regulation via Cys1483., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2020
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39. Analytical and clinical validation of rapid chemiluminescence enzyme immunoassay for urinary thioredoxin, an oxidative stress-dependent early biomarker of acute kidney injury.
- Author
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Yokoi S, Kasuno K, Nishimori K, Nishikawa S, Nishikawa Y, Morita S, Kobayashi M, Fukushima S, Mikami D, Takahashi N, Oota Y, Kimura H, Soya Y, Kimata S, Nishimura K, Ono T, Muso E, Yoshida H, Yodoi J, and Iwano M
- Subjects
- Acute Kidney Injury diagnosis, Adult, Aged, Biomarkers urine, Female, Humans, Immunoenzyme Techniques, Male, Middle Aged, Oxidative Stress, Acute Kidney Injury urine, Luminescence, Thioredoxins urine
- Abstract
Background: Oxidative stress is now recognized to be an important therapeutic target in kidney diseases. However, there are currently no biomarkers that can be used clinically to diagnose renal oxidative stress., Methods: A rapid assay system for urinary thioredoxin 1, an oxidative stress-dependent biomarker of acute kidney injury (AKI), was developed as a chemiluminescence enzyme immunoassay and validated analytically and clinically., Results: Analytic evaluation revealed that hemolytic hemoglobin caused measurements to be abnormally high, above the detectable range. However, urine sediment containing red blood cells did not affect the measurements. Assays using our proposed chemiluminescence enzyme immunoassay were completed within as little as 6 min, whereas a conventional ELISA > 4 h. Aciduria
- Published
- 2020
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40. Cochlear supporting cells function as macrophage-like cells and protect audiosensory receptor hair cells from pathogens.
- Author
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Hayashi Y, Suzuki H, Nakajima W, Uehara I, Tanimura A, Himeda T, Koike S, Katsuno T, Kitajiri SI, Koyanagi N, Kawaguchi Y, Onomoto K, Kato H, Yoneyama M, Fujita T, and Tanaka N
- Subjects
- Animals, Animals, Newborn, Escherichia coli immunology, Hair Cells, Auditory, Inner cytology, Hair Cells, Auditory, Outer cytology, Immunity, Innate, Interferon-alpha biosynthesis, Interferon-alpha immunology, Interferon-beta biosynthesis, Interferon-beta immunology, Labyrinth Supporting Cells cytology, Labyrinth Supporting Cells drug effects, Labyrinth Supporting Cells virology, Lipopolysaccharides pharmacology, Macrophages cytology, Macrophages drug effects, Macrophages virology, Mice, Mice, Inbred ICR, Organ Culture Techniques, Phagocytosis drug effects, Saccharomyces cerevisiae immunology, Spiral Ganglion cytology, Stria Vascularis cytology, Theilovirus growth & development, Theilovirus pathogenicity, Hair Cells, Auditory, Inner physiology, Hair Cells, Auditory, Outer physiology, Labyrinth Supporting Cells immunology, Macrophages immunology, Spiral Ganglion physiology, Stria Vascularis physiology
- Abstract
To protect the audiosensory organ from tissue damage from the immune system, the inner ear is separated from the circulating immune system by the blood-labyrinth barrier, which was previously considered an immune-privileged site. Recent studies have shown that macrophages are distributed in the cochlea, especially in the spiral ligament, spiral ganglion, and stria vascularis; however, the direct pathogen defence mechanism used by audiosensory receptor hair cells (HCs) has remained obscure. Here, we show that HCs are protected from pathogens by surrounding accessory supporting cells (SCs) and greater epithelial ridge (GER or Kölliker's organ) cells (GERCs). In isolated murine cochlear sensory epithelium, we established Theiler's murine encephalomyelitis virus, which infected the SCs and GERCs, but very few HCs. The virus-infected SCs produced interferon (IFN)-α/β, and the viruses efficiently infected the HCs in the IFN-α/β receptor-null sensory epithelium. Interestingly, the virus-infected SCs and GERCs expressed macrophage marker proteins and were eliminated from the cell layer by cell detachment. Moreover, lipopolysaccharide induced phagocytosis of the SCs without cell detachment, and the SCs phagocytosed the bacteria. These results reveal that SCs function as macrophage-like cells, protect adjacent HCs from pathogens, and provide a novel anti-infection inner ear immune system.
- Published
- 2020
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41. Anti-Allergic and Anti-Inflammatory Effects and Molecular Mechanisms of Thioredoxin on Respiratory System Diseases.
- Author
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Zhou J, Wang C, Wu J, Fukunaga A, Cheng Z, Wang J, Yamauchi A, Yodoi J, and Tian H
- Subjects
- Animals, Anti-Allergic Agents administration & dosage, Anti-Inflammatory Agents, Non-Steroidal administration & dosage, Cytokines antagonists & inhibitors, Cytokines biosynthesis, Humans, Inflammation metabolism, Inflammation pathology, Protective Agents chemistry, Respiratory Tract Infections metabolism, Respiratory Tract Infections pathology, Thioredoxins administration & dosage, Thioredoxins genetics, Anti-Allergic Agents pharmacology, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Inflammation drug therapy, Protective Agents pharmacology, Respiratory Tract Infections drug therapy, Thioredoxins metabolism
- Abstract
Significance: The pathogenesis and progression of allergic inflammation in the respiratory system are closely linked to oxidative stress. Thioredoxin (TRX) is an essential redox balance regulator in organisms and is induced by various oxidative stress factors, including ultraviolet rays, radiation, oxidation, viral infections, ischemia reperfusion, and anticancer agents. Recent Advances: We demonstrated that systemic administration and transgenic overexpression of TRX is useful in a wide variety of in vivo inflammatory respiratory diseases models, such as viral pneumonia, interstitial lung disease, chronic obstructive pulmonary disease, asthma, acute respiratory distress syndrome, and obstructive sleep apnea syndrome, by removing reactive oxygen species, blocking production of inflammatory cytokines, inhibiting migration and activation of neutrophils and eosinophils, and regulating the cellular redox status. In addition, TRX's anti-inflammatory mechanism is different from the mechanisms associated with anti-inflammatory agents, such as glucocorticoids, which regulate the inflammatory reaction in association with suppressing immune responses. Critical Issues: Understanding the molecular mechanism of TRX is very helpful for understanding the role of TRX in respiratory diseases. In this review, we show the protective effect of TRX in various respiratory diseases. In addition, we discuss its anti-allergic and anti-inflammatory molecular mechanism in detail. Future Directions: The application of TRX may be useful for treating respiratory allergic inflammatory disorders. Antioxid. Redox Signal . 32, 785-801.
- Published
- 2020
- Full Text
- View/download PDF
42. Influenza virus NS1- C/EBPβ gene regulatory complex inhibits RIG-I transcription.
- Author
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Kumari R, Guo Z, Kumar A, Wiens M, Gangappa S, Katz JM, Cox NJ, Lal RB, Sarkar D, Fisher PB, García-Sastre A, Fujita T, Kumar V, Sambhara S, Ranjan P, and Lal SK
- Subjects
- A549 Cells, Binding Sites, CCAAT-Enhancer-Binding Protein-beta, DEAD Box Protein 58 immunology, Host Microbial Interactions genetics, Humans, Influenza A virus immunology, Influenza, Human virology, Phosphorylation, Promoter Regions, Genetic, Receptors, Immunologic, Transcription, Genetic, Viral Nonstructural Proteins genetics, DEAD Box Protein 58 genetics, Gene Expression Regulation, Immunity, Innate, Influenza A virus genetics, Viral Nonstructural Proteins immunology
- Abstract
Influenza virus non-structural protein 1 (NS1) counteracts host antiviral innate immune responses by inhibiting Retinoic acid inducible gene-I (RIG-I) activation. However, whether NS1 also specifically regulates RIG-I transcription is unknown. Here, we identify a CCAAT/Enhancer Binding Protein beta (C/EBPβ) binding site in the RIG-I promoter as a repressor element, and show that NS1 promotes C/EBPβ phosphorylation and its recruitment to the RIG-I promoter as a C/EBPβ/NS1 complex. C/EBPβ overexpression and siRNA knockdown in human lung epithelial cells resulted in suppression and activation of RIG-I expression respectively, implying a negative regulatory role of C/EBPβ. Further, C/EBPβ phosphorylation, its interaction with NS1 and occupancy at the RIG-I promoter was associated with RIG-I transcriptional inhibition. These findings provide an important insight into the molecular mechanism by which influenza NS1 commandeers RIG-I transcriptional regulation and suppresses host antiviral responses., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest with the contents of this article. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of Centers for Disease Control and Prevention., (Published by Elsevier B.V.)
- Published
- 2020
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43. Epigenetic regulation affects gene amplification in Drosophila development.
- Author
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Kohzaki H, Asano M, Murakami Y, and Mazo A
- Subjects
- Animals, Animals, Genetically Modified, Chorion growth & development, Chorion metabolism, Drosophila Proteins genetics, Drosophila Proteins metabolism, Drosophila melanogaster growth & development, Drosophila melanogaster metabolism, Female, Histones metabolism, Humans, Methylation, Oogenesis genetics, Origin Recognition Complex genetics, Origin Recognition Complex metabolism, Ovarian Follicle cytology, Ovarian Follicle growth & development, Ovarian Follicle metabolism, Receptors, Steroid genetics, Receptors, Steroid metabolism, Drosophila melanogaster genetics, Epigenesis, Genetic, Gene Amplification, Gene Expression Regulation, Developmental
- Abstract
In Drosophila melanogaster, in response to developmental transcription factors, and by repeated initiation of DNA replication of four chorion genes, ovarian follicle cells, form an onion skin-type structure at the replication origins. The DNA replication machinery is conserved from yeast to humans. Subunits of the origin recognition complex (ORC) is comprised of Orc1, Orc2, and Cdc6 genes. While mutations of Orc1 and Orc2 and not Cdc6can be lethal, overexpression of these genes lead to female sterility. Ecdysone, is a steroidal prohormone of the major insect molting hormone 20-hydroxyecdysone that in Drosophila, triggers molting, metamorphosis, and oogenesis. To this end, we identified several ecdysone receptor (EcR) binding sites around gene amplification loci. We also found that H3K4 was trimethylated at chorion gene amplification origins, but not at the act1 locus. Female mutants overexpressing Lsd1 (a dimethyl histone H3K4 demethylase) or Lid (a trimethyl histone H3K4 demethylase), but not a Lid mutant, were sterile. The data suggest that ecdysone signaling determines which origin initiates DNA replication and contributes to the development. Screening strategies using Drosophila offer the opportunity for development of drugs that reduce gene amplification and alter histone modification associated with epigenetic effects.
- Published
- 2020
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44. Corrigendum to "Susceptibility of domestic animals to pseudotype virus bearing RD-114 virus envelope protein" [Gene 567(2) (2015) 189-195].
- Author
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Miyaho RN, Nakagawa S, Hashimoto-Gotoh A, Nakaya Y, Shimode S, Sakaguchi S, Yoshikawa R, Takahashi MU, and Miyazawa T
- Published
- 2019
- Full Text
- View/download PDF
45. G9a-dependent histone methylation can be induced in G1 phase of cell cycle.
- Author
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Fukuda M, Sakaue-Sawano A, Shimura C, Tachibana M, Miyawaki A, and Shinkai Y
- Subjects
- Animals, Cell Line, Female, Geminin metabolism, Humans, Lysine metabolism, Methylation, Mice, Knockout, Mitosis, G1 Phase, Histone-Lysine N-Methyltransferase metabolism, Histones metabolism
- Abstract
Epigenetic information (epigenome) on chromatin is crucial for the determination of cellular identity and for the expression of cell type-specific biological functions. The cell type-specific epigenome is maintained beyond replication and cell division. Nucleosomes of chromatin just after DNA replication are a mixture of old histones with the parental epigenome and newly synthesized histones without such information. The diluted epigenome is mostly restored within one cell cycle using the epigenome on the parental DNA and nucleosomes as replication templates. However, many important questions about the epigenome replication process remain to be clarified. In this study, we investigated the model system comprising of dimethylated histone H3 lysine 9 (H3K9me2) and its regulation by the lysine methyltransferase G9a. Using this epigenome model system, we addressed whether H3K9me2 can be induced in specific cell cycle stages, especially G1. Using cell cycle-specific degrons, we achieved G1 or late G1-to M phases specific accumulation of exogenous G9a in G9a deficient cells. Importantly, global levels of H3K9me2 were significantly recovered by both cell types. These data indicate that H3K9me2 may be plastic and inducible, even in the long-living, terminally-differentiated, post-mitotic, G0-G1 cell population in vivo. This knowledge is valuable in designing epigenome-manipulation-based treatments for diseases.
- Published
- 2019
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46. Endoplasmic reticulum-mediated induction of interleukin-8 occurs by hepatitis B virus infection and contributes to suppression of interferon responsiveness in human hepatocytes.
- Author
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Tsuge M, Hiraga N, Zhang Y, Yamashita M, Sato O, Oka N, Shiraishi K, Izaki Y, Makokha GN, Uchida T, Kurihara M, Nomura M, Tsushima K, Nakahara T, Murakami E, Abe-Chayama H, Kawaoka T, Miki D, Imamura M, Kawakami Y, Aikata H, Ochi H, Hayes CN, Fujita T, and Chayama K
- Subjects
- Animals, Cells, Cultured, Hepatitis B, Chronic immunology, Hepatocytes metabolism, Humans, Liver metabolism, Mice, Stress, Physiological, Up-Regulation, Endoplasmic Reticulum metabolism, Hepatitis B virus physiology, Hepatitis B, Chronic metabolism, Hepatocytes virology, Interleukin-8 metabolism
- Abstract
The events in the immune response to hepatitis B virus (HBV) remain unclear. We analyzed the direct influence of HBV on gene expression in human hepatocytes under immunodeficient conditions using a human hepatocyte chimeric mouse model. HBV-infected or non-infected chimeric mouse livers were collected, and gene expression profiles were compared. Since IL-8 was the most significantly up-regulated gene at 8 weeks after HBV infection, we focused on IL-8 and found that HBx and the large HBs (L-HBs) protein induce transcription of IL-8 via endoplasmic reticulum stress. This stress induces IL-8 transcription via NFAT activation and contributes to suppression of interferon responsiveness in HBV-infected human hepatocytes. In the present study, we identified a novel regulatory mechanism in which the L-HBs protein activates IL-8 via endoplasmic reticulum stress, suggesting a key role for IL-8 in the immune response to HBV and a potential new target for antiviral treatments of HBV infection., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
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47. Interferon stimulation creates chromatin marks and establishes transcriptional memory.
- Author
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Kamada R, Yang W, Zhang Y, Patel MC, Yang Y, Ouda R, Dey A, Wakabayashi Y, Sakaguchi K, Fujita T, Tamura T, Zhu J, and Ozato K
- Subjects
- Animals, Bone Marrow Cells cytology, Cell Division genetics, Chromatin genetics, Chromatin immunology, Histones genetics, Histones immunology, Interferon-beta genetics, Macrophages cytology, Mice, Mice, Mutant Strains, RNA Polymerase II genetics, RNA Polymerase II immunology, Signal Transduction genetics, Transcription Factors genetics, Transcription Factors immunology, Bone Marrow Cells immunology, Cell Division immunology, Epigenesis, Genetic immunology, Immunity, Innate, Interferon-beta immunology, Macrophages immunology, Signal Transduction immunology, Transcription, Genetic immunology
- Abstract
Epigenetic memory for signal-dependent transcription has remained elusive. So far, the concept of epigenetic memory has been largely limited to cell-autonomous, preprogrammed processes such as development and metabolism. Here we show that IFNβ stimulation creates transcriptional memory in fibroblasts, conferring faster and greater transcription upon restimulation. The memory was inherited through multiple cell divisions and led to improved antiviral protection. Of ∼2,000 IFNβ-stimulated genes (ISGs), about half exhibited memory, which we define as memory ISGs. The rest, designated nonmemory ISGs, did not show memory. Surprisingly, mechanistic analysis showed that IFN memory was not due to enhanced IFN signaling or retention of transcription factors on the ISGs. We demonstrated that this memory was attributed to accelerated recruitment of RNA polymerase II and transcription/chromatin factors, which coincided with acquisition of the histone H3.3 and H3K36me3 chromatin marks on memory ISGs. Similar memory was observed in bone marrow macrophages after IFNγ stimulation, suggesting that IFN stimulation modifies the shape of the innate immune response. Together, external signals can establish epigenetic memory in mammalian cells that imparts lasting adaptive performance upon various somatic cells., Competing Interests: The authors declare no conflict of interest.
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- 2018
- Full Text
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48. Sfh1, an essential component of the RSC chromatin remodeling complex, maintains genome integrity in fission yeast.
- Author
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Kotomura N, Tsunemine S, Kuragano M, Asanuma T, Nakagawa H, Tanaka K, and Murakami Y
- Subjects
- Cell Cycle Proteins genetics, Cell Cycle Proteins metabolism, Centromere, Chromosomal Proteins, Non-Histone genetics, Chromosomal Proteins, Non-Histone metabolism, Chromosome Segregation, Heterochromatin, Mutation, Retroelements, Schizosaccharomyces pombe Proteins genetics, Cohesins, Chromatin Assembly and Disassembly, Gene Expression Regulation, Fungal, Genomic Instability, Schizosaccharomyces genetics, Schizosaccharomyces pombe Proteins metabolism
- Abstract
Abp1 is a fission yeast CENP-B homologue that contributes to centromere function, silencing at pericentromeric heterochromatin and silencing of retrotransposons. We identified the sfh1 gene, encoding a core subunit of the fission yeast chromatin remodeling complex RSC as an Abp1-interacting protein. Because sfh1 is essential for growth, we isolated temperature-sensitive sfh1 mutants. These mutants showed defects in centromere functions, reflected by sensitivity to an inhibitor of spindle formation and minichromosome instability. Sfh1 localized at both kinetochore and pericentromeric heterochromatin regions. Although sfh1 mutations had minor effect on silencing at these regions, they decreased the levels of cohesin on centromeric heterochromatin. Sfh1 also localized at a retrotransposon, Tf2, in a partly Abp1-dependent manner, and assisted in silencing of Tf2 by Abp1 probably in the same pathway as a histone chaperon, HIRA, which is also known to involve in Tf2 repression. Furthermore, sfh1 mutants were sensitive to several DNA-damaging treatments (HU, MMS, UV and X-ray). Increase in spontaneous foci of Rad22, a recombination Mediator protein Rad52 homologue, in sfh1 mutant suggests that RSC functions in homologous recombination repair of double-stranded break downstream of the Rad22 recruitment. These results indicate that RSC plays multiple roles in the maintenance of genome integrity., (© 2018 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.)
- Published
- 2018
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49. Targeting the HTLV-I-Regulated BATF3/IRF4 Transcriptional Network in Adult T Cell Leukemia/Lymphoma.
- Author
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Nakagawa M, Shaffer AL 3rd, Ceribelli M, Zhang M, Wright G, Huang DW, Xiao W, Powell J, Petrus MN, Yang Y, Phelan JD, Kohlhammer H, Dubois SP, Yoo HM, Bachy E, Webster DE, Yang Y, Xu W, Yu X, Zhao H, Bryant BR, Shimono J, Ishio T, Maeda M, Green PL, Waldmann TA, and Staudt LM
- Subjects
- Animals, Basic-Leucine Zipper Transcription Factors physiology, Cell Line, Tumor, Genes, myc, Humans, Mice, Proteins antagonists & inhibitors, Retroviridae Proteins physiology, Basic-Leucine Zipper Transcription Factors genetics, Gene Regulatory Networks, Human T-lymphotropic virus 1 physiology, Interferon Regulatory Factors genetics, Leukemia-Lymphoma, Adult T-Cell genetics
- Abstract
Adult T cell leukemia/lymphoma (ATLL) is a frequently incurable disease associated with the human lymphotropic virus type I (HTLV-I). RNAi screening of ATLL lines revealed that their proliferation depends on BATF3 and IRF4, which cooperatively drive ATLL-specific gene expression. HBZ, the only HTLV-I encoded transcription factor that is expressed in all ATLL cases, binds to an ATLL-specific BATF3 super-enhancer and thereby regulates the expression of BATF3 and its downstream targets, including MYC. Inhibitors of bromodomain-and-extra-terminal-domain (BET) chromatin proteins collapsed the transcriptional network directed by HBZ and BATF3, and were consequently toxic for ATLL cell lines, patient samples, and xenografts. Our study demonstrates that the HTLV-I oncogenic retrovirus exploits a regulatory module that can be attacked therapeutically with BET inhibitors., (Published by Elsevier Inc.)
- Published
- 2018
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50. Translational Control of Sox9 RNA by mTORC1 Contributes to Skeletogenesis.
- Author
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Iezaki T, Horie T, Fukasawa K, Kitabatake M, Nakamura Y, Park G, Onishi Y, Ozaki K, Kanayama T, Hiraiwa M, Kitaguchi Y, Kaneda K, Manabe T, Ishigaki Y, Ohno M, and Hinoi E
- Subjects
- Animals, Cell Differentiation genetics, Gene Expression, Mice, Mice, Transgenic, Phenotype, SOX9 Transcription Factor metabolism, Skeleton embryology, Mechanistic Target of Rapamycin Complex 1 metabolism, Osteogenesis genetics, Protein Biosynthesis, SOX9 Transcription Factor genetics, Skeleton metabolism
- Abstract
The mechanistic/mammalian target of rapamycin complex 1 (mTORC1) regulates cellular function in various cell types. Although the role of mTORC1 in skeletogenesis has been investigated previously, here we show a critical role of mTORC1/4E-BPs/SOX9 axis in regulating skeletogenesis through its expression in undifferentiated mesenchymal cells. Inactivation of Raptor, a component of mTORC1, in limb buds before mesenchymal condensations resulted in a marked loss of both cartilage and bone. Mechanistically, we demonstrated that mTORC1 selectively controls the RNA translation of Sox9, which harbors a 5' terminal oligopyrimidine tract motif, via inhibition of the 4E-BPs. Indeed, introduction of Sox9 or a knockdown of 4E-BP1/2 in undifferentiated mesenchymal cells markedly rescued the deficiency of the condensation observed in Raptor-deficient mice. Furthermore, introduction of the Sox9 transgene rescued phenotypes of deficient skeletal growth in Raptor-deficient mice. These findings highlight a critical role of mTORC1 in mammalian skeletogenesis, at least in part, through translational control of Sox9 RNA., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
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