Influence of the genetic heterogeneity of the ISDR and PePHD regions of hepatitis C virus on the response to interferon therapy in chronic hepatitis C

Two genomic regions of hepatitis C virus (HCV), the interferon sensitivity- determining region (ISDR) of the non-structural 5A gene (NS5A) and the prot ein kinase-RNA activated (PKR)-eukariotic transcription factor (eIF2-alpha) phosphorylation homology domain (PePHD) of the structural E2 gene, interac t in vitro with the interferon-inducible cellular PKR protein kinase. Mutat ions within these regions might, therefore, influence the response to inter feron therapy. Viral load at baseline and sequence heterogeneity of HCV in NS5A and E2 regions was studied in 74 HCV-1b and in 12 HCV-3a infected pati ents with chronic hepatitis C who were treated with interferon. As previous ly reported by us, in a smaller series of patients in which the ISDR region was analyzed [Saiz et al. (1998) Journal Infectious Diseases 177:839-847], in the present study a low viral load and a high number of amino acid muta tions within the ISDR, but not within the PePHD region, were significantly associated with long-term response to interferon among HCV-1b infected pati ents. No relationship between these viral features and response to therapy was disclosed in patients infected with HCV-3a. (C) 2001 Wiley-Liss, Inc.