Hepatitis C virus (HCV) is a major pathogen causing liver diseases. It has been known that HCV interacts with cell surface receptors through the viral protein complexes composed of the viral envelop glycoproteins E1 and E2. Recent studies revealed that HCV enters host cells through clathrin-mediated endocytosis pathway. Disabled-2 (Dab2) is a cargo-specific adaptor protein, which modulate clathrin-coat assembly at plasma membrane by synchronizing cargo selection and lattice polymerization events. To determine whether Dab2 involved in HCV entry, RNA interference technology was performed to deplete endogenous Dab2 expression in Huh7.5 cells followed by infection with HCV pseudotyped virus (HCVpv). Our data revealed that HCVpv infection was decreased in Dab2 knockdown cells. The reduced infectivity could be compensated by overexpression of Dab2 but not another clathrin adaptor molecule autosomal recessive hypercholesterolemia (ARH) in Dab2 knockdown stable cells. Moreover, Dab2 colocalized with HCV core protein in clathrin coated vesicle during HCV cell culture viral particle (HCVcc) infection. To advance investigate the functional domain of Dab2 involved in HCV entry, the deleted or mutated Dab2 was constructed. The data demonstrated that the PTB domain but not myosin VI binding motif of Dab2 was essential for HCV entry. Taken together, our results suggest that Dab2 plays an important role in HCV entry into host cells.
