Hepatitis C virus exploits cyclophilin A to evade PKR

eLife

Greg J Towers¹  Sophie Ridewood²  Che C Colpitts³  David L Selwood⁴  Caitlin F Ng⁴  Justin Warne⁵  Bethany Schneiderman⁵  Ralf Bartenschlager⁵  Keisuke Tabata⁶ 

[1] Division Virus-Associated Carcinogenesis, German Cancer Research Center, Heidelberg, Germany;Division of Infection and Immunity, University College London, London, United Kingdom;Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, Canada;Department of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany;Division of Infection and Immunity, University College London, London, United Kingdom;Wolfson Institute for Biomedical Research, UCL, London, United Kingdom;

关键词: virus-host interactions;    innate antiviral immunity;    viral evasion;    hepatitis C virus;    cyclophilin A;    protein kinase R;   

DOI  :  10.7554/eLife.52237

来源: DOAJ

【 摘 要 】

Counteracting innate immunity is essential for successful viral replication. Host cyclophilins (Cyps) have been implicated in viral evasion of host antiviral responses, although the mechanisms are still unclear. Here, we show that hepatitis C virus (HCV) co-opts the host protein CypA to aid evasion of antiviral responses dependent on the effector protein kinase R (PKR). Pharmacological inhibition of CypA rescues PKR from antagonism by HCV NS5A, leading to activation of an interferon regulatory factor-1 (IRF1)-driven cell intrinsic antiviral program that inhibits viral replication. These findings further the understanding of the complexity of Cyp-virus interactions, provide mechanistic insight into the remarkably broad antiviral spectrum of Cyp inhibitors, and uncover novel aspects of PKR activity and regulation. Collectively, our study identifies a novel antiviral mechanism that harnesses cellular antiviral immunity to suppress viral replication.

【 授权许可】

Unknown