Processing and functions of hepatitis C virus proteins

Hepatitis C virus (HCV) has a positive-stranded RNA genome of about 9.5 kb and a large open reading frame encoding a precursor polyprotein of ca. 3,00 0 amino acids (aa). This polyprotein is cleaved by host cellular signalase( s) and viral proteases into 10 viral proteins in the order of NH2-Core-E1 - E2-p7-NS2-NS3-NS4A-NS4B-NS5A-NS5B-COOH. Core and E1/E2 are considered to be a capsid protein and envelope glycoproteins, respectively. NS2-NS5B are pu tative nonstructural proteins involved in the replication of HCV. NS2/3 is a metalloprotease which cleaves in cis at the NS2/3 junction. NS3 possesses serine protease and RNA helicase activities and is responsible for the cle avage of the remaining nonstructural proteins. NS4A is suggested to be a co factor for NS3 protease, Although the function of p7, NS4B and NS5A are sti ll unknown, an association of a mutation in NS5A with a susceptibility to i nterferon (IFN) has been reported. NS5B possesses an RNA-dependent RNA poly merase activity. Most of the current findings in HCV proteins depend on exp ression studies of HCV cDNA clones because of the lack of an efficient repl ication system in cell cultures. Therefore, a final assignment of cleavages and functions of HCV proteins has to await the propagation of HCV in cell cultures.