Cellular microRNA networks regulate host dependency of hepatitis C virus infection.

Abstract:

:Cellular microRNAs (miRNAs) have been shown to regulate hepatitis C virus (HCV) replication, yet a systematic interrogation of the repertoire of miRNAs impacting HCV life cycle is lacking. Here we apply integrative functional genomics strategies to elucidate global HCV-miRNA interactions. Through genome-wide miRNA mimic and hairpin inhibitor phenotypic screens, and miRNA-mRNA transcriptomics analyses, we identify three proviral and nine antiviral miRNAs that interact with HCV. These miRNAs are functionally linked to particular steps of HCV life cycle and related viral host dependencies. Further mechanistic studies demonstrate that miR-25, let-7, and miR-130 families repress essential HCV co-factors, thus restricting viral infection at multiple stages. HCV subverts the antiviral actions of these miRNAs by dampening their expression in cell culture models and HCV-infected human livers. This comprehensive HCV-miRNA interaction map provides fundamental insights into HCV-mediated pathogenesis and unveils molecular pathways linking RNA biology to viral infections.

journal_name

Nat Commun

journal_title

Nature communications

authors

Li Q,Lowey B,Sodroski C,Krishnamurthy S,Alao H,Cha H,Chiu S,El-Diwany R,Ghany MG,Liang TJ

doi

10.1038/s41467-017-01954-x

subject

Has Abstract

pub_date

2017-11-27 00:00:00

pages

1789

issue

1

issn

2041-1723

pii

10.1038/s41467-017-01954-x

journal_volume

8

pub_type

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