Control of hepatitis C virus replication in mouse liver-derived cells by MAVS-dependent production of type I and type III interferons.

2.50
Hdl Handle:
http://hdl.handle.net/10033/554178
Title:
Control of hepatitis C virus replication in mouse liver-derived cells by MAVS-dependent production of type I and type III interferons.
Authors:
Anggakusuma; Frentzen, Anne; Gürlevik, Engin; Yuan, Qinggong; Steinmann, Eike; Ott, Michael; Staeheli, Peter; Schmid-Burgk, Jonathan; Schmidt, Tobias; Hornung, Veit; Kuehnel, Florian; Pietschmann, Thomas
Abstract:
Hepatitis C virus (HCV) efficiently infects only humans and chimpanzees. Although the detailed mechanisms responsible for this narrow species tropism remain elusive, recent evidence has shown that murine innate immune responses efficiently suppress HCV replication. Therefore, poor adaptation of HCV to evade and/or counteract innate immune responses may prevent HCV replication in mice. The HCV NS3-4A protease cleaves human MAVS, a key cellular adaptor protein required for RIG-I-like receptor (RLR)-dependent innate immune signaling. However, it is unclear if HCV interferes with mouse MAVS function equally well. Moreover, MAVS-dependent signaling events that restrict HCV replication in mouse cells were incompletely defined. Thus, we quantified the ability of HCV NS3-4A to counteract mouse and human MAVS. HCV NS3-4A similarly diminished both human and mouse MAVS-dependent signaling in human and mouse cells. Moreover, replicon-encoded protease cleaved a similar fraction of both MAVS variants. Finally, FLAG-tagged MAVS proteins repressed HCV replication to similar degrees. Depending on MAVS expression, HCV replication in mouse liver cells triggered not only type I but also type III IFNs, which cooperatively repressed HCV replication. Mouse liver cells lacking both type I and III IFN receptors were refractory to MAVS-dependent antiviral effects, indicating that the HCV-induced MAVS-dependent antiviral state depends on both type I and III IFN receptor signaling.
Affiliation:
Institute of Experimental Virology, Twincore Centre for Experimental and Clinical Infection Research, Hanover, Germany.
Citation:
Control of hepatitis C virus replication in mouse liver-derived cells by MAVS-dependent production of type I and type III interferons. 2015, 89 (7):3833-45 J. Virol.
Journal:
Journal of virology
Issue Date:
Apr-2015
URI:
http://hdl.handle.net/10033/554178
DOI:
10.1128/JVI.03129-14
PubMed ID:
25609814
Type:
Article
Language:
en
ISSN:
1098-5514
Appears in Collections:
publications of the department experimental Virology([TC]EVIR)

Full metadata record

DC FieldValue Language
dc.contributor.authorAnggakusumaen
dc.contributor.authorFrentzen, Anneen
dc.contributor.authorGürlevik, Enginen
dc.contributor.authorYuan, Qinggongen
dc.contributor.authorSteinmann, Eikeen
dc.contributor.authorOtt, Michaelen
dc.contributor.authorStaeheli, Peteren
dc.contributor.authorSchmid-Burgk, Jonathanen
dc.contributor.authorSchmidt, Tobiasen
dc.contributor.authorHornung, Veiten
dc.contributor.authorKuehnel, Florianen
dc.contributor.authorPietschmann, Thomasen
dc.date.accessioned2015-05-19T15:19:36Zen
dc.date.available2015-05-19T15:19:36Zen
dc.date.issued2015-04en
dc.identifier.citationControl of hepatitis C virus replication in mouse liver-derived cells by MAVS-dependent production of type I and type III interferons. 2015, 89 (7):3833-45 J. Virol.en
dc.identifier.issn1098-5514en
dc.identifier.pmid25609814en
dc.identifier.doi10.1128/JVI.03129-14en
dc.identifier.urihttp://hdl.handle.net/10033/554178en
dc.description.abstractHepatitis C virus (HCV) efficiently infects only humans and chimpanzees. Although the detailed mechanisms responsible for this narrow species tropism remain elusive, recent evidence has shown that murine innate immune responses efficiently suppress HCV replication. Therefore, poor adaptation of HCV to evade and/or counteract innate immune responses may prevent HCV replication in mice. The HCV NS3-4A protease cleaves human MAVS, a key cellular adaptor protein required for RIG-I-like receptor (RLR)-dependent innate immune signaling. However, it is unclear if HCV interferes with mouse MAVS function equally well. Moreover, MAVS-dependent signaling events that restrict HCV replication in mouse cells were incompletely defined. Thus, we quantified the ability of HCV NS3-4A to counteract mouse and human MAVS. HCV NS3-4A similarly diminished both human and mouse MAVS-dependent signaling in human and mouse cells. Moreover, replicon-encoded protease cleaved a similar fraction of both MAVS variants. Finally, FLAG-tagged MAVS proteins repressed HCV replication to similar degrees. Depending on MAVS expression, HCV replication in mouse liver cells triggered not only type I but also type III IFNs, which cooperatively repressed HCV replication. Mouse liver cells lacking both type I and III IFN receptors were refractory to MAVS-dependent antiviral effects, indicating that the HCV-induced MAVS-dependent antiviral state depends on both type I and III IFN receptor signaling.en
dc.language.isoenen
dc.titleControl of hepatitis C virus replication in mouse liver-derived cells by MAVS-dependent production of type I and type III interferons.en
dc.typeArticleen
dc.contributor.departmentInstitute of Experimental Virology, Twincore Centre for Experimental and Clinical Infection Research, Hanover, Germany.en
dc.identifier.journalJournal of virologyen

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