microRNA-99a Restricts Replication of Hepatitis C Virus by Targeting mTOR and de novo Lipogenesis

Viruses. 2020 Jun 27;12(7):696. doi: 10.3390/v12070696.

Abstract

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.

Keywords: hepatitis C virus; lipid droplet; mTOR; microRNA-99a; viral replication.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Down-Regulation
  • Gene Expression Regulation
  • Hepacivirus / genetics
  • Hepacivirus / physiology*
  • Hepatocytes / virology
  • Humans
  • Lipogenesis / genetics*
  • MicroRNAs / blood
  • MicroRNAs / genetics*
  • Signal Transduction
  • Sterol Regulatory Element Binding Protein 1 / genetics
  • TOR Serine-Threonine Kinases / genetics*
  • Virus Replication / genetics*

Substances

  • MIRN99 microRNA, human
  • MicroRNAs
  • Sterol Regulatory Element Binding Protein 1
  • MTOR protein, human
  • TOR Serine-Threonine Kinases