VARIATION IN THE HEPATITIS-C VIRUS NS5A REGION IN RELATION TO HYPERVARIABLE REGION-1 HETEROGENEITY DURING INTERFERON TREATMENT

The putative interferon sensitivity determining region (ISDR) in the N S5a region of the hepatitis C virus (HCV) was analyzed in '73 interfer on alpha (IFN-alpha) treated patients representing genotypes 1a, 1b, a nd 2b. These patients had previously been followed longitudinally duri ng treatment with respect to viral load and to virus heterogeneity usi ng the hypervariable region 1 (HVR1) sequence as a marker. In the pres ent study, the NS5a region was analyzed for nonresponders and sustaine d responders using direct DNA sequencing. While the previous results o f analyzing viral composition and load showed evidence of selection, n o corresponding selection of specific NS5a ISDR sequences was observed in the nonresponders, and identical ISDR sequences were observed amon g both sustained responders and nonresponders. Thus, we cannot verify a correlation between ISDR sequence and the observed selection of IFN- alpha-resistant quasispecies demonstrated as a restriction of HVR1 het erogeneity. This indicates that the potential for using ISDR as a diag nostic or prognostic marker during IFN-alpha treatment is limited. J. Med. Virol. 56:33-38, 1998. (C) 1998 Wiley-Liss, Inc.