Molecular biology and the diagnosis and treatment of liver diseases

Figure 1 Schematic diagram of the HCV genome and proteins. The positive stranded RNA of about 10000 nucleotides is translated into a polyprotein of approximately 3000 amino acids. This polyprotein is proteolytically cleaved into several smaller proteins. Core, E1 and E2 are structural polypeptides. Core protein is the virus nucleocapsid and E1 and E2 are viral envelope proteins. A small polypeptide known as P7 (not shown) is also produced by additional cleavage between E2 and NS2. The major non-structural proteins are NS2, NS3, NS4 and NS5. NS4 is further processed into NS4A and NS4B and NS5 into NS5A and NS5B. NS2 and part of NS3 are proteases that process the viral polyprotein. NS3 also has RNA helicase activity. NS4A is a cofactor for the NS3 protease and NS5B is an RNA-dependent, RNA polymerase. The functions of NS4B and NS5A are less well understood but NS5A is thought to play a role in determining sensitivity to interferon.