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- Title
microRNA-99a Restricts Replication of Hepatitis C Virus by Targeting mTOR and De Novo Lipogenesis.
- Authors
Lee, Eun Byul; Sung, Pil Soo; Kim, Jung-Hee; Park, Dong Jun; Hur, Wonhee; Yoon, Seung Kew
- 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.
- Subjects
HEPATITIS C virus; LIPID synthesis; MICRORNA; CARRIER proteins
- Publication
Viruses (1999-4915), 2020, Vol 12, Issue 7, p696
- ISSN
1999-4915
- Publication type
Article
- DOI
10.3390/v12070696