Amino acid substitutions in NS5A region of GB virus C and response to interferon therapy

GB virus C (GBV-C) is related to hepatitis C virus (HCV) and has a similar genomic structure. Some predictors for the efficacy of interferon (IFN) the rapy on HCV have been reported: genotype, viral load, IFN dose, and the ami no acid substitutions in the NS5A region, designated as the interferon sens itivity determining region (ISDR). To evaluate the correlation between the amino acid substitutions in the GBV-C NS5A region and the response to IFN t herapy, single-strand conformation polymorphism (SSCP) analysis was perform ed in the 12 concomitantly GBV-C-and HCV-infected patients who received IFN therapy at three time points: before, endpoint, and after the IFN therapy. The region in the GBV-C NS5A studied includes the amino acids that exhibit some homology to the ISDR and the various substitutions. By SSCP analysis, amplicons were separated into 1-4 bands, which indicated the existence of heterogeneity in each host. However, the deduced amino acid sequences in th ese bands exhibited no characteristic differences among these strains irres pective of response to IFN therapy. Of the 32 strains separated by SSCP, 7 strains were responders, and 25 were nonresponders. The mean amino acid sub stitution, compared with the consensus sequence of nonresponders, was 1.00 +/- 0.93 among responders, and 1.40 +/- 0.85 among nonresponders (P= NS). N o correlation between the amino acid sequence in the GBV-C NS5A region and response to IFN therapy was found, indicating that the GBV-C NS5A region do se not act as the ISDR. (C) 1999 Wiley-Liss, Inc.