Control of hepatitis C virus replication in mouse liver-derived cells by MAVS-dependent production of type I and type III interferons.
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Authors
AnggakusumaFrentzen, Anne
Gürlevik, Engin
Yuan, Qinggong
Steinmann, Eike
Ott, Michael
Staeheli, Peter
Schmid-Burgk, Jonathan
Schmidt, Tobias
Hornung, Veit
Kuehnel, Florian
Pietschmann, Thomas
Issue Date
2015-04
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Show full item recordAbstract
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.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.Affiliation
Institute of Experimental Virology, Twincore Centre for Experimental and Clinical Infection Research, Hanover, Germany.Journal
Journal of virologyPubMed ID
25609814Type
ArticleLanguage
enISSN
1098-5514ae974a485f413a2113503eed53cd6c53
10.1128/JVI.03129-14
Scopus Count
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