Frequency of Interferon-Resistance Conferring Substitutions in Amino Acid Positions 70 and 91 of Core Protein of the Russian HCV 1b Isolates Analyzed in the T-Cell Epitopic Context

V. S. Kichatova, K. K. Kyuregyan, N. V. Soboleva, A. A. Karlsen, O. V. Isaeva, M. G. Isaguliants, M. I. Mikhailov

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6 Citations (Scopus)

Abstract

Amino acid substitutions R70Q/H and L91M in HCV subtype 1b core protein can affect the response to interferon and are associated with the development of hepatocellular carcinoma. We found that the rate of R70Q/H in HCV 1b from Russia was 31.2%, similar to that in HCV strains from Asia (34.0%), higher than that in the European (18.0%, p=0.0010), but lower than that in the US HCV 1b strains (62.8%, p<0.0001). Substitution L91M was found in 80.4% of the Russian HCV 1b isolates, higher than in Asian isolates (43.8%, p<0.0001). Thus, a significant proportion of Russian HCV 1b isolates carry the unfavorable R70Q/H and/or L91M substitution. In silico analysis of the epitopic structure of the regions of substitutions revealed that both harbor clusters of T-cell epitopes. Peptides encompassing these regions were predicted to bind to a panel of HLA class I molecules, with substitutions impairing peptide recognition by HLA I molecules of the alleles prevalent in Russia. This indicates that HCV 1b with R70Q/H and L91M substitutions may have evolved as the immune escape variants. Impairment of T-cell recognition may play a part in the negative effect of these substitutions on the response to IFN treatment.

Original languageEnglish
Article number7685371
JournalJournal of Immunology Research
Volume2018
DOIs
Publication statusPublished - 2018

Field of Science

  • 3.2 Clinical medicine

Publication Type

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

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