The protein kinase-interacting domain in the hepatitis C virus envelope glycoprotein-2 gene is highly conserved in genotype 1-infected patients treated with interferon

The hepatitis C virus (HCV) envelope glycoprotein-2 inhibits the interferon (IFN)-induced, double-stranded RNA-activated protein kinase (PKR) via the PKR eukaryotic initiation factor-2 alpha phosphorylation homology domain (P ePHD). The present study examined the genetic variability of the PePHD in p atients receiving IFN therapy. The PePHD from 12 HCV genotype 1 (HCV-1)-inf ected patients receiving daily IFN therapy was amplified by reverse-transcr iptase polymerase chain reaction and analyzed by direct and clonal sequenci ng. The PePHD was highly conserved in 38 HCV GenBank isolates. There was no difference in pretreatment PePHD sequences isolated from IFN responders ve rsus nonresponders. The major PePHD quasi-species variant did not change af ter 6 weeks of daily IFN therapy, and in 1 patient the major quasi-species variant did not change during 9 months of observation. Sequencing of 25 pre treatment PePHD clones from 3 patients confirmed that there was extremely l ow sequence variability surrounding the PePHD. The PePHD is highly conserve d in HCV-1-infected IFN responders and nonresponders and does not appear to evolve in response to IFN therapy.