Alcohol-induced autophagy via upregulation of PIASy promotes HCV replication in human hepatoma cells.

摘要: Both alcohol and hepatitis C virus (HCV) infection could induce cellular autophagy in liver cells, which is considered to be essential for productive HCV replication. However, whether alcohol-induced involved the pathogenesis of still poorly understood. Alcohol treatment Huh7 cells (a hepatoma cell line that supports JFH-1 replication), evidenced by increase LC3B-II levels, conversion LC3B-I LC3B-II, formation GFP-LC3 puncta as well decrease p62 level alcohol-treated compared with control cells. also significantly increased PIASy member PIAS family) expression, can act a SUMO (small ubiquitin-like modifier protein) E3 ligase regulate broader range processes including autophagy. Overexpression or silencing expression autophagic activation caused treatment, respectively, thus affect replication correspondingly. In absence alcohol, overexpression autophagy, judged changes levels presence chloroquine (CQ), lysosome inhibitor. More importantly, 3-methyladenine (3-MA), an inhibitor early stage effects on were largely blocked. Furthermore, selectively drive accumulation SUMO1-conjugated proteins, along upregulation several important factors, ATG7 ATG5-ATG12. conclusion, promotes through partly attributes its induction expression. PIASy-enhanced proteins may contribute inducing effect Our findings provide novel mechanism action alcohol-promoting context