Cellular microRNA networks regulate host dependency of hepatitis C virus infection

Adult 0301 basic medicine Sulfonamides Science Biopsy Gene Expression Profiling Q Genomics Hepacivirus Isoquinolines Virus Replication Hepatitis C Article 3. Good health MicroRNAs Young Adult 03 medical and health sciences Liver Cell Line, Tumor Host-Pathogen Interactions Humans RNA, Messenger
DOI: 10.1038/s41467-017-01954-x Publication Date: 2017-11-21T11:38:01Z
ABSTRACT
AbstractCellular 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.
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