microRNA-99a Restricts Replication of Hepatitis C Virus by Targeting mTOR and de novo Lipogenesis.
Viruses
; 12(7)2020 06 27.
Article
in En
| MEDLINE
| ID: mdl-32605105
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Virus Replication
/
Hepacivirus
/
MicroRNAs
/
Lipogenesis
/
TOR Serine-Threonine Kinases
Limits:
Humans
Language:
En
Journal:
Viruses
Year:
2020
Document type:
Article
Publication country:
CH
/
SUIZA
/
SUÍÇA
/
SWITZERLAND