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Open AccessArticle

microRNA-99a Restricts Replication of Hepatitis C Virus by Targeting mTOR and De Novo Lipogenesis

1
The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
2
Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul 06591, Korea
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Viruses 2020, 12(7), 696; https://doi.org/10.3390/v12070696
Received: 28 May 2020 / Revised: 22 June 2020 / Accepted: 24 June 2020 / Published: 27 June 2020
(This article belongs to the Special Issue MicroRNAs and Other Small RNAs in Viral Infections)
In this study, we investigated the role of microRNA-99a (miR-99a) in hepatitis C virus (HCV) replication and lipogenesis in hepatocytes. Cell-culture-derived HCV (HCVcc) infection caused down-regulation of miR-99a in Huh-7 cells, and the relative levels of miR-99a were significantly lower in the sera of the HCV-infected patients than in those of healthy controls. Transfection of miR-99a-5p mimics resulted in a decrease in the intracellular and secreted HCV RNA levels. It also caused a decreased mammalian target of rapamycin (mTOR) protein level and phosphorylation of its downstream targets in HCV-replicating cells. Sterol regulatory element binding protein (SREBP)-1c expression and intracellular lipid accumulation decreased when either miR-99a-5p mimics or si-mTOR was transfected in oleic acid-treated Huh-7 cells. Overexpression of mTOR rescued HCV RNA replication and lipid droplet accumulation in miR-99a-5p mimics-transfected HCV replicon cells. Our data demonstrated that miR-99a ameliorates intracellular lipid accumulation by regulating mTOR/SREBP-1c and causes inefficient replication and packaging of intracellular HCV. View Full-Text
Keywords: hepatitis C virus; microRNA-99a; lipid droplet; mTOR; viral replication hepatitis C virus; microRNA-99a; lipid droplet; mTOR; viral replication
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MDPI and ACS Style

Lee, E.B.; Sung, P.S.; Kim, J.-H.; Park, D.J.; Hur, W.; Yoon, S.K. microRNA-99a Restricts Replication of Hepatitis C Virus by Targeting mTOR and De Novo Lipogenesis. Viruses 2020, 12, 696.

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