Genetic Drifts in PKR-EIF2A Phosphorylation Homology Domain Region in Iranian HCV Positive Patients during Interferon Therapy

Hepatitis C virus (HCV) envelope glycoprotein-2 could block elF2 phosphorylation with PKR suppression and in this way stops IFN pathway activation via homology domain with phosphorylation site of elF2-PKR (PePHD) in its C-terminal. In some studies, mutations in PePHD region have been shown to be associated with sustained response to IFN. Present study examined the genetic variability of the PePHD in patients receiving IFN therapy.The PePHD from HCV genotype 1a/1b infected patients receiving IFN was amplified by reverse transcriptase polymerase chain reaction ( RT-PCR) and analyzed using bidirectional sequencing. The PePHD sequence was different in pretreatment isolates from that of three months treated patients. The sequencing data were analyzed by Clustal X, MEGA and Bio Edit soft wares. The finding indicated that the major PePHD quasispecies could change after three months IFN therapy and in one patient; the major PePHD quasispecies could change after six months IFN therapy. These mutations were occurred in codons 665, 666, 667 of followed-up samples and in codons 660, 661, 666, 670 of randomly treated patients. Some of these mutations were similar to those reported by prior studies. Other mutations were also detected at up and downstream regions of PePHD which could have influenced the structure, conformation and configuration of this region and thereby suppressing PePHD inhibitory properties. Thus our data suggested that HCV E2 PePHD may play an important role in determining the interferon response.