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 cell factors in viral proliferation. Using a large-capacity next-generation sequencing method, the present inventors analyzed changes in host transcripts and identified 30 candidate genes up-regulated in HCVcc (cell culture-grown HCV) infected cells. Among the candidate genes, Rab32 was selected and studied intensively. Rab32 is a small GTPase that modulates various intracellular membrane-trafficking in a variety of cell types. In the present invention, we have found that Rab32 mRNA and protein levels are increased in HCV-infected cells and that GTP-binding Rab32, which mainly expresses HCV infection, is converted into GDP-binding Rab32 to contribute to Rab32 aggressiveness, . In addition, GDP-binding Rab32 selectively interacted with the HCV core to position the core within the Rab32-induced coagulation structure of the perinuclear region, which appears to be the viral assembly site. Using RNA inhibition technology, we found that Rab32 is not required for the other stages of the HCV life cycle but is required for the assembly phase. Taken together, these data indicate that HCV modulates Rab32 activity to facilitate virus assembly.