E1 and E2 glycoproteins form a heterodimer which is involved in virus attachment to the host cell, virion internalization via clathrin-dependent endocytosis and fusion with host membrane. E1/E2 heterodimer binds to human LDLR, CD81 and SCARB1/SR-BI receptors, however this binding insufficient for infection, some additional liver specific cofactors may be required. The fusion function may perhaps be conducted by E1. E2 hinders human EIF2AK2/PKR activation, preventing the establishment of an antiviral state. E2 is a viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively located on dendritic cells (DCs), and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses. These interactions allow seizure of circulating HCV particles by these cells and subsequent diffusion to permissive cells.
