Rab32 Pharmaceutical composition for prevention and treatment for Hepatitis C containing Rab32 expression or activity inhibitors

摘要

Hepatitis C virus (HCV) is highly dependent on host cellular factors for viral propagation. Using high-throughput next-generation sequencing, the present inventors analyzed the host transcriptomic changes and identified 30 candidate genes which were upregulated in cell culture-grown HCV (HCVcc)-infected cells. Of these candidates, the present inventors selected Rab32 for further investigation. Rab32 is a small GTPase that regulates a variety of intracellular membrane-trafficking events in various cell types. In the present invention, the present inventors demonstrated that both mRNA and protein levels of Rab32 were increased in HCV-infected cells, and further showed that HCV infection converted the predominantly expressed GTP-bound Rab32 to GDP-bound Rab32, contributing to the aggregation of Rab32 and subsequently making it less sensitive to cellular degradation machinery. In addition, GDP-bound Rab32 selectively interacted with HCV core and deposited the core into Rab32-derived aggregated structures in the perinuclear region, which were likely to be viral assembly sites. By using RNA interference technology, the present inventors demonstrated that Rab32 was required for the assembly stage but not for other stages of the HCV life cycle. Taken together, these data suggest that HCV may modulate Rab32 activity to facilitate virus assembly.