A CENTRAL HYDROPHOBIC DOMAIN OF THE HEPATITIS-C VIRUS NS4A PROTEIN ISNECESSARY AND SUFFICIENT FOR THE ACTIVATION OF THE NS3 PROTEASE

The processing at the NS3/4A, NS4A/4B, NS4B/5A and NS5A/5B junctions i n the non-structural region of the hepatitis C virus (HCV) polyprotein is performed by a viral serine protease activity contained within the N-terminal 180 amino acids of the NS3 protein. Full protease activity is only achieved upon the interaction of a region at the N terminus o f NS3 with the NS4A protein, this region is also involved in the modul ation of the protease activity. Using the rabbit reticulocyte expressi on system, we have defined the minimal domain of NS4A that is necessar y to increase the cleavage efficiency of NS3. A synthetic peptide cont aining the same region, NS4A amino acids 21 to 32, stimulates the prot eolytic activity of NS3 at all the trans-cleavage sites.