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Eukaryotic translation initiation factor 4All contributes to microRNA-122 regulation of hepatitis C virus replication

Ahmed, Choudhary-Shoaib; Winlow, Poppy L.; Parsons, Aimee L.; Jopling, Catherine L.

Eukaryotic translation initiation factor 4All contributes to microRNA-122 regulation of hepatitis C virus replication Thumbnail


Authors

Choudhary-Shoaib Ahmed

Poppy L. Winlow

Aimee L. Parsons



Abstract

Hepatitis C virus (HCV) is a positive sense RNA virus that persistently infects human liver, leading to cirrhosis and hepatocellular carcinoma. HCV replication requires the liver-specific microRNA-122 (miR-122). In contrast to canonical miRNA-mediated repression via 3’UTR sites, miR-122 positively regulates HCV replication by a direct interaction with the 5’ untranslated region (UTR) of the viral RNA. The protein factor requirements for this unusual miRNA regulation remain poorly understood. Here, we identify eIF4AII, previously implicated in miRNA-mediated repression via 3’UTR sites, as a host factor that is important for HCV replication. We demonstrate that eIF4AII interacts with HCV RNA and that this interaction is miR-122-dependent. We show that effective miR-122 binding to, and regulation of, HCV RNA are reduced following eIF4AII depletion. We find that the previously identified HCV co-factor CNOT1, which has also been implicated in miRNA-mediated repression via 3’UTR sites, contributes to regulation of HCV by eIF4AII. Finally, we show that eIF4AI knockdown alleviates the inhibition of HCV replication mediated by depletion of either eIF4AII or CNOT1. Our results suggest a competition effect between the eIF4A proteins to influence HCV replication by modulation of miR-122 function.

Journal Article Type Article
Acceptance Date Mar 28, 2018
Online Publication Date Apr 14, 2018
Publication Date Jul 6, 2018
Deposit Date Apr 16, 2018
Publicly Available Date Apr 16, 2018
Journal Nucleic Acids Research
Print ISSN 0305-1048
Electronic ISSN 1362-4962
Publisher Oxford University Press
Peer Reviewed Peer Reviewed
Volume 46
Issue 12
DOI https://doi.org/10.1093/nar/gky262
Public URL https://nottingham-repository.worktribe.com/output/945407
Publisher URL https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gky262/4970503

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