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Hepatitis C virus exploits cyclophilin A to evade PKR

Colpitts, CC; Ridewood, S; Schneiderman, B; Warne, J; Tabata, K; Ng, CF; Bartenschlager, R; ... Towers, GJ; + view all (2020) Hepatitis C virus exploits cyclophilin A to evade PKR. eLife , 9 , Article e52237. 10.7554/eLife.52237. Green open access

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Abstract

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.

Type: Article
Title: Hepatitis C virus exploits cyclophilin A to evade PKR
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.7554/eLife.52237
Publisher version: https://doi.org/10.7554/eLife.52237
Language: English
Additional information: © 2020, Colpitts et al. This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/).
Keywords: cyclophilin A, hepatitis C virus, immunology, infectious disease, inflammation, innate antiviral immunity, microbiology, protein kinase R, viral evasion, virus, virus-host interactions
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Wolfson Inst for Biomedical Research
URI: https://discovery.ucl.ac.uk/id/eprint/10102180
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