Cellular microRNA networks regulate host dependency of hepatitis C virus infection

Qisheng Li; Brianna Lowey; Catherine Sodroski; Siddharth Krishnamurthy; Hawwa Alao; Helen Cha; Stephan Chiu; Ramy El-Diwany; Marc G Ghany; T Jake Liang

doi:10.1038/s41467-017-01954-x

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Cellular microRNA networks regulate host dependency of hepatitis C virus infection

Journal article

Peer reviewed

Cellular microRNA networks regulate host dependency of hepatitis C virus infection

Qisheng Li, Brianna Lowey, Catherine Sodroski, Siddharth Krishnamurthy, Hawwa Alao, Helen Cha, Stephan Chiu, Ramy El-Diwany, Marc G Ghany and T Jake Liang

Nature communications, Vol.8(1), pp.1789-16

11/27/2017

DOI: 10.1038/s41467-017-01954-x

PMCID: PMC5702611

PMID: 29176620

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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.

Adult

Biopsy

Cell Line, Tumor

Gene Expression Profiling - methods

Genomics - methods

Hepacivirus - physiology

Hepatitis C - drug therapy

Hepatitis C - genetics

Hepatitis C - pathology

Hepatitis C - virology

Host-Pathogen Interactions - genetics

Humans

Isoquinolines - therapeutic use

Liver - pathology

MicroRNAs - metabolism

RNA, Messenger - metabolism

Sulfonamides - therapeutic use

Virus Replication - genetics

Young Adult

Details

Title: Subtitle: Cellular microRNA networks regulate host dependency of hepatitis C virus infection
Creators: Qisheng Li - National Institute of Diabetes and Digestive and Kidney Diseases
Brianna Lowey - National Institute of Diabetes and Digestive and Kidney Diseases
Catherine Sodroski - National Institute of Diabetes and Digestive and Kidney Diseases
Siddharth Krishnamurthy - National Institute of Diabetes and Digestive and Kidney Diseases
Hawwa Alao - National Institute of Diabetes and Digestive and Kidney Diseases
Helen Cha - National Institute of Diabetes and Digestive and Kidney Diseases
Stephan Chiu - National Institute of Diabetes and Digestive and Kidney Diseases
Ramy El-Diwany - National Institute of Diabetes and Digestive and Kidney Diseases
Marc G Ghany - National Institute of Diabetes and Digestive and Kidney Diseases
T Jake Liang - National Institute of Diabetes and Digestive and Kidney Diseases
Resource Type: Journal article
Publication Details: Nature communications, Vol.8(1), pp.1789-16
DOI: 10.1038/s41467-017-01954-x
PMID: 29176620
PMCID: PMC5702611
NLM abbreviation: Nat Commun
ISSN: 2041-1723
eISSN: 2041-1723
Grant note: HHSN276201200017C / NLM NIH HHS T32 GM007309 / NIGMS NIH HHS Z99 DK999999 / Intramural NIH HHS
Language: English
Date published: 11/27/2017
Academic Unit: Surgery
Record Identifier: 9984966751202771

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