1. Hepatitis E Virus Infects Neurons and Brains
- Author
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Qiuwei Pan, Femke M.S. de Vrij, Laurent Alric, Ane C Ayo-Martin, Yijin Wang, Eleonora Aronica, Jeroen J.J. van Eijk, Wanlu Cao, Manzhi Zhao, Xinying Zhou, Maikel P. Peppelenbosch, Wenshi Wang, Nassim Kamar, Fen Huang, Bart C. Jacobs, Mark van der Kroeg, Yuebang Yin, Zhanmin Lin, Harry R. Dalton, Chris I. De Zeeuw, Jean-Marie Peron, Robert A. de Man, Lei Xu, Herold J. Metselaar, Steven A. Kushner, Dave Sprengers, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Kunming University of Science and Technology (KMUST), Département de Gastroentérologie, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Jeroen Bosch Ziekenhuis, Department of Pathology [Amsterdam, the Netherlands], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Netherlands Institute for Neuroscience (NIN), Royal Netherlands Academy of Arts and Sciences (KNAW), Royal Cornwall Hospital, University of Exeter, Gastroenterology & Hepatology, Neurosciences, Psychiatry, Immunology, Neurology, ANS - Cellular & Molecular Mechanisms, Pathology, APH - Mental Health, APH - Aging & Later Life, Pôle Maladies de l'appareil digestif [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), and Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)
- Subjects
0301 basic medicine ,viruses ,[SDV]Life Sciences [q-bio] ,Alpha interferon ,hepatitis E virus ,Biology ,medicine.disease_cause ,Virus ,cerebrospinal fluid ,03 medical and health sciences ,chemistry.chemical_compound ,Hepatitis E virus ,SDG 3 - Good Health and Well-being ,peripheral nervous system ,medicine ,Journal Article ,Immunology and Allergy ,Viral shedding ,Hepatitis ,Ribavirin ,virus diseases ,Hepatitis E ,medicine.disease ,central nervous system ,Virology ,digestive system diseases ,3. Good health ,030104 developmental biology ,Infectious Diseases ,chemistry ,Viral replication - Abstract
International audience; Hepatitis E virus (HEV), as a hepatotropic virus, is supposed to exclusively infect the liver and only cause hepatitis. However, a broad range of extrahepatic manifestations (in particular, idiopathic neurological disorders) have been recently reported in association with its infection. In this study, we have demonstrated that various human neural cell lines (embryonic stem cell-derived neural lineage cells) induced pluripotent stem cell-derived human neurons and primary mouse neurons are highly susceptible to HEV infection. Treatment with interferon-α or ribavirin, the off-label antiviral drugs for chronic hepatitis E, exerted potent antiviral activities against HEV infection in neural cells. More importantly, in mice and monkey peripherally inoculated with HEV particles, viral RNA and protein were detected in brain tissues. Finally, patients with HEV-associated neurological disorders shed the virus into cerebrospinal fluid, indicating a direct infection of their nervous system. Thus, HEV is neurotropic in vitro, and in mice, monkeys, and possibly humans. These results challenge the dogma of HEV as a pure hepatotropic virus and suggest that HEV infection should be considered in the differential diagnosis of idiopathic neurological disorders.
- Published
- 2017
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