Figure 1.

Schematic representation of the cell-free hepatitis C virus (HCV) entry pathway. This cartoon summarizes the host factors and sequence of events leading from initial viral attachment of lipo-viro particles (LVPs) to HCV internalization and release of the viral genome in the cytosol of hepatocytes. The initial binding step primarily involving the lipoprotein component of LVPs likely is a rather unspecific event, which results in the concentration of the virus at the basolateral membrane of hepatocytes and exposure of viral envelope glycoprotein domains that enable the virus to specifically interact with SR-BI, CD81, and CLDN1 (post-binding). The formation of an HCV co-receptor complex is essential for subsequent viral internalization via clathrin-mediated and dynamin-dependent endocytosis. This process is highly regulated by various kinases. Endocytotic vesicles ultimately mature into acidic endosomes, thus promoting low pH-dependent HCV fusion.