The amino acid sequence of the PKR-eIF2alpha phosphorylation homology domain of hepatitis C virus envelope 2 protein and response to interferon-alpha.

Abstract

A region of the hepatitis C virus (HCV) envelope 2 protein, the protein kinase, PKR and early initiation factor 2alpha phosphorylation homology domain (PePHD), may be important in interferon (IFN)-alpha resistance. The PePHD was amplified by polymerase chain reaction and sequenced, and the amino acid sequence derived from pretreatment serum of 14 genotype 3-infected patients with a range of responses to IFN-alpha therapy. Only 1 patient had a PePHD variant. IFN-resistant PePHD variants present at low titers in pretreatment serum should be selected by therapy; therefore, the PePHD amino acid sequence was also obtained from serum collected during or after treatment in 5 patients with breakthrough or relapse of HCV RNA positivity. No difference was found between the pre- and posttreatment PePHD sequences. Thus, it appears that pretreatment sequencing of the PePHD would not enable clinicians to predict the treatment response. There was no evidence that IFN therapy exerts selection pressure in this region.