Activation of the unfolded protein response and autophagy after hepatitis C virus infection suppresses innate antiviral immunity in vitro

Ke, P.Y., and Chen, S.S. J Clin Invest. 2011;121:37-56.

Speaker: Yen-Wei Wu (吳彥緯)                                    Time: 14:10~15:00, Jun. 8, 2011

Commentator: Bei-Chang Yang, Ph.D.(楊倍昌老師)  Place: Room 601

Abstract

Autophagy, a cellular metabolism system for degradation of cytoplasmic proteins and organelles, was reported to be involved in modulation of viral infection and host defence. However, the detail mechenisms of autophagy in modulating viral replication are still unclear. Infection of hepatitic C virus (HCV), a membrane-enveloped virus with positive single-strand RNA, causes chronic hepatic disease. In this study, the authors demonstrate that HCV induces unfolded protein reponse (UPR) and complete autophagic flux to facilitate viral RNA replication in human hepatoma cells. Knockdown of UPR modulators or autophagy-related genes will inhibit RNA replication of HCV and enhance interferon β antiviral response. The 3‘-UTR and PU/UC of HCV RNA are required for this UPR-autophagy response related IFN-β down-regulation. Both inducers of UPR and autophagy can supress HCV or dengue virus pathogen associated molecular pattern (PAMP)-induced IFN-β activation. In summary, the authors first reported that HCV induces UPR-autophagy response to help viral replication by inhibition of innate immunity.

References

1.          Lee DY, Lee J, Sugden B. The unfolded protein response and autophagy: herpesviruses rule! J Virol. 2009;83(3):1168–1172.

2.          Sir D, Chen WL, Choi J, Wakita T, Yen TS, Ou JH. Induction of incomplete autophagic response by hepatitis C virus via the unfolded protein response. Hepatology. 2008;48(4):1054–1061.