miR-148a and miR-30a limit HCV-dependent suppression of the lipid droplet protein, ADRP, in HCV infected cell models

Loading...
Thumbnail Image

Date

2017

Journal Title

Journal ISSN

Volume Title

Type

Article

Publisher

John Wiley and Sons Inc.

Series Info

Journal of Medical Virology
89

Scientific Journal Rankings

Abstract

Hepatitis C Virus (HCV) promotes lipid droplet (LD) formation and perturbs the expression of the LD associated PAT proteins ADRP and TIP47, to promote its own lifecycle. HCV enhances TIP47 and suppresses ADRP by displacing it from LD surface in infected cell models. We have previously shown that suppression of TIP47 by miR-148a and miR-30a decreased intracellular LDs and HCV RNA. Thus, this study aimed at examining whether this microRNA-mediated suppression of HCV would limit HCV-dependent displacement of ADRP from LDs. ADRP expression was examined in 21 HCV-infected liver biopsies and 9 healthy donor liver tissues as well as in HCV-infected Huh7 cells using qRT-PCR. miR-148a and miR-30a expression was manipulated using specific oligos in JFH-1 infected, oleic acid treated cells, to study their impact on ADRP expression using qRT-PCR, and immunofluorescence microscopy. Intracellular HCV RNA was assessed using qRT-PCR. ADRP is down regulated in patients as well as HCVcc-JFH-I infected cell models. Forcing the expression of both miRNAs induced ADRP on the mRNA and protein levels. This study shows that HCV suppresses hepatic ADRP expression in infected patients and cell lines. Forcing the expression of miR-148a and miR-30a limits the suppressive effect of HCV on ADRP. J. Med. Virol. 89:653 659, 2017. 2016 Wiley Periodicals, Inc. 2016 Wiley Periodicals, Inc.

Description

Scopus

Keywords

lipids, liver, microRNAs, PAT proteins, viral infection, adipophilin, mannose 6 phosphate receptor binding protein 1, microRNA, microRNA 148a, microRNA 30a, unclassified drug, virus RNA, adipophilin, mannose 6 phosphate receptor binding protein 1, microRNA, MIRN148 microRNA, human, MIRN30 microRNA, human, PLIN2 protein, human, PLIN3 protein, human, virus RNA, ADRP gene, adult, aged, Article, clinical article, controlled study, down regulation, female, gene expression, gene function, hepatitis C, human, human cell, human tissue, immunofluorescence microscopy, male, middle aged, protein expression, reverse transcription polymerase chain reaction, antagonists and inhibitors, biopsy, cell line, fluorescence microscopy, gene expression profiling, Hepacivirus, hepatitis C, host pathogen interaction, liver, liver cell, metabolism, pathogenicity, pathology, real time polymerase chain reaction, virology, Adult, Biopsy, Cell Line, Female, Gene Expression Profiling, Hepacivirus, Hepatitis C, Hepatocytes, Host-Pathogen Interactions, Humans, Liver, Male, MicroRNAs, Microscopy, Fluorescence, Middle Aged, Perilipin-2, Perilipin-3, Real-Time Polymerase Chain Reaction, RNA, Viral

Citation

Full Text link