The amino acid sequence of the PKR-eIF2 alpha phosphorylation homology domain of hepatitis C virus envelope 2 protein and response to interferon-alpha

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