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.
| Original language | English |
|---|---|
| Article number | 696 |
| Journal | Viruses |
| Volume | 12 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 2020 |
Bibliographical note
Funding Information:Funding: This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) and funded by the Ministry of Science, ICT and Future Planning (2015R1C1A1 A02037212 and 2019R1I1A1A01059642). This research was partly supported by the Research Fund of Seoul St. Mary’s Hospital, The Catholic University of Korea.
Publisher Copyright:
© 2020 by the authors.
Keywords
- Hepatitis C virus
- Lipid droplet
- MTOR
- MicroRNA-99a
- Viral replication
