title: Antiviral Activities of Different Interferon Types and Subtypes against Hepatitis E Virus Replication.
abstract: Hepatitis E virus (HEV) is the causative agent of hepatitis E in humans and a member of the genusOrthohepevirusin the familyHepeviridae HEV infections are the common cause of acute hepatitis but can also take chronic courses. Ribavirin is the treatment of choice for most patients, and type I interferon (IFN) has been evaluated in a few infected transplant patientsin vivo In this study, the antiviral effects of different exogenously administered interferons were investigated by using state-of-the-art subgenomic replicon and full-length HEV genome cell culture models. Hepatitis C virus (HCV) subgenomic replicons based on the genotype 2a JFH1 isolate served as the reference. The experiments revealed that HEV RNA replication was inhibited by the application of all types of IFN, including IFN-α (type I), IFN-γ (type II), and IFN-λ3 (type III), but to a far lesser extent than HCV replication. Simultaneous determination of interferon-stimulated gene (ISG) expression levels for all IFN types demonstrated efficient downregulation by HEV. Furthermore, different IFN-α subtypes were also able to block viral replication in combination with ribavirin. The IFN-α subtypes 2a and 2b exerted the strongest antiviral activity against HEV. In conclusion, these data demonstrate for the first time moderate anti-HEV activities of types II and III IFNs and different IFN-α subtypes. As HEV employed a potent anti-interferon mechanism by restricting ISG expression, exogenous application of IFNs as immunotherapy should be carefully assessed.
authors.affiliation: Institute for Experimental Virology, Twincore Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Todt
authors.affiliation: EA4294, Laboratoire de Virologie, Centre Hospitalier Universitaire et Universite de Picardie Jules Verne, Amiens, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: François
authors.affiliation: Institute for Experimental Virology, Twincore Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
authors.lastname: Anggakusuma
authors.affiliation: Institute for Experimental Virology, Twincore Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Behrendt
authors.affiliation: Institute for Experimental Virology, Twincore Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Engelmann
authors.affiliation: Institute for Experimental Virology, Twincore Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
authors.forename: Leonard
authors.initials: L
authors.lastname: Knegendorf
authors.affiliation: Institute for Experimental Virology, Twincore Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Vieyres
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
authors.affiliation: Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
authors.forename: Rune
authors.initials: R
authors.lastname: Hartmann
authors.affiliation: Institute for Experimental Virology, Twincore Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pietschmann
authors.affiliation: EA4294, Laboratoire de Virologie, Centre Hospitalier Universitaire et Universite de Picardie Jules Verne, Amiens, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Duverlie
authors.affiliation: Institute for Experimental Virology, Twincore Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany eike.steinmann@twincore.de.
authors.forename: Eike
authors.initials: E
authors.lastname: Steinmann
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000998:Antiviral Agents / Q000494:pharmacology*; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D054357:Chemokine CXCL10 / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D005838:Genotype; D056945:Hep G2 Cells; D016752:Hepatitis E virus / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D054884:Host-Pathogen Interactions; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D007372:Interferons; D007378:Interleukins / Q000235:genetics / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins / Q000494:pharmacology; D012093:Replicon / Q000187:drug effects; D012254:Ribavirin / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects*; D000095022:Interferon Lambda
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000998:Antiviral Agents; D002352:Carrier Proteins; D054357:Chemokine CXCL10; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007371:Interferon-gamma; D007372:Interferons; D007378:Interleukins; D047908:Intracellular Signaling Peptides and Proteins; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D012254:Ribavirin; C114753:CXCL10 protein, human; C484290:IFIT1 protein, human; C116468:IFIT3 protein, human; C000624353:interferon-lambda, human; D000095022:Interferon Lambda