Akt1 is required to maintain lipid droplets for release of HCV infectious virions

Abstract Hepatitis C virus (HCV) relies on the interplay of viral and host factors to complete its life cycle. It has evolved to benefit from Akt activation at some point in the life cycle through a variety of mechanisms. Our preliminary result showed that Akt-specific inhibitor reduced cell culture-derived HCV (HCVcc) infectivity in a dose-dependent manner. To dissect the mechanism, we adopted a two-part cell culture-derived HCV infection protocol with Akt1 small interfering RNAs (siRNAs) to determine the role of Akt in the HCV life cycle. The result showed that Akt1 was a crucial host factor involved in the late stage of HCV life cycle. Akt1 depletion reduced viral particles released from Huh-7.5.1 cells to culture medium with consequent reduction of viral reinfection in cell culture system, which was restored by ectopic Akt1 expression. To further study the mechanism, we found that Akt1 enhanced lipogenic pathway through transcriptional activation of fatty acid synthase (FAS) by sterol regulatory element binding protein-1 (SREBP1) to maintain sufficient lipid droplet that is an essential organelle for assembly and release of HCV infectious virions.