GB VIRUS-B AND HEPATITIS-C VIRUS NS3 SERINE PROTEASES SHARE SUBSTRATE-SPECIFICITY

GB virus B (GBV-B) is a recently discovered virus responsible for hepa titis in tamarins (Saguinus species), GBV-B belongs to the Flavivirida e family and is closely related to the human pathogen hepatitis C viru s (HCV). Nonstructural protein 3 (NS3) of HCV has been shown to encomp ass a serine protease domain required for viral maturation. GBV-B and HCV share only about 30% of the amino acid sequence within the NS3 pro tease domain, The catalytic triad is conserved, and the residue Phe-15 4, presumed to be a crucial amino acid for determining the S-1 specifi city pocket of the HCV NS3 protease, is also conserved, We have expres sed a synthetic gene encoding the GBV-B NS3 protease domain in Escheri chia coli and have characterized the purified recombinant protein for its activity on HCV substrates, We have shown that the NS3 region of t he GBV-B genome actually encodes a serine protease that, despite the l ow sequence homology, shares substrate specificity with the HCV NS3 pr otease.