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

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 sup...

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Published in:Journal of medical virology 2017-04, Vol.89 (4), p.653-659
Main Authors: El‐Ekiaby, Nada M., Mekky, Radwa Y., Riad, Sarah E., Elhelw, Dalia S., El‐Sayed, Mohammed, Esmat, Gamal, Abdelaziz, Ahmed I.
Format: Article
Language:English
Subjects:
Adult
Biopsy
Cell Line
Cells
Female
Gene Expression Profiling
Hepacivirus - pathogenicity
Hepatitis
Hepatitis C - pathology
Hepatitis C virus
Hepatocytes - virology
Host-Pathogen Interactions
Humans
Lipids
liver
Liver - pathology
Male
microRNAs
MicroRNAs - metabolism
Microscopy, Fluorescence
Middle Aged
PAT proteins
Perilipin-2 - antagonists & inhibitors
Perilipin-3 - metabolism
Protein expression
Real-Time Polymerase Chain Reaction
RNA, Viral - analysis
viral infection
Virology
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Summary: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.
ISSN:0146-6615
1096-9071
DOI:10.1002/jmv.24677