Cellular microRNA networks regulate host dependency of hepatitis C virus infection

• DOI: 10.1038/s41467-017-01954-x
• Publication Date: 2017-11-21T11:38:01Z
• Authors: Qisheng Li; Brianna Lowey; Catherine Sodroski; Siddharth Krishna...; Hawwa Alao; Helen Cha; Stephan Chiu; Ramy El-Diwany; Marc G. Ghany; T. Jake Liang
• Keywords: Viral life cycle; Viral Pathogenesis

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