Mutations in two PKR-binding domains in chronic hepatitis C of genotype 3a and correlation with viral loads and interferon responsiveness

Shouichi Yokozaki, Yoshiaki Katano, Kazuhiko Hayashi, Masatoshi Ishigami, Akihiro Itoh, Yoshiki Hirooka, Isao Nakano, Hidemi Goto

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8 Citations (Scopus)


Interferon (IFN) induces the double-stranded RNA-dependent protein kinase (PKR) to inhibit viral replication. Two motifs of the PKR-binding domain exist in the E2 and the NS5A regions of the hepatitis C virus (HCV). These regions are called the PKR-eukaryotic transcription factor (elF2-alpha) phosphorylation homology domain (PePHD), and the IFN sensitivity-determining region (ISDR). Both regions are inhibited by PKR. Thus, several studies have reported the relationship between these regions and IFN responsiveness and the HCV viral load. However, the data obtained from these studies remain controversial. The aim of this study was to investigate the genomic heterogeneity of the PePHD and the ISDR in patients with genotype 3a and how this impacts HCV replication and the response to IFN therapy. Twenty-one male patients infected with HCV genotype 3a were studied. The PePHD was well conserved, and mutations were found in only one amino acid position in two patients. Patients with three or more mutations in the ISDR had lower viral loads than those with fewer than two mutations (192.2±176.7 vs. 1279.4±997.6KIU/ml, P=0.0277). Ten (71.4%) of 14 patients achieved a sustained virological response to IFN therapy. No specific amino acid substitutions in the PePHD and the ISDR were associated with IFN responsiveness; however, the number of mutations in the ISDR was significantly associated with the HCV viral load. The findings from this study suggest that the ISDR plays an important role in regulating viral replication in patients infected with HCV genotype 3a.

Original languageEnglish
Pages (from-to)1727-1732
Number of pages6
JournalJournal of Medical Virology
Issue number10
Publication statusPublished - 10-2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Virology
  • Infectious Diseases


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