Analysis of resistance-associated substitutions in hepatitis C virus sequences from Kyrgyzstan

Abstract

Introduction. The countries of Central Asia, including Kyrgyzstan, are characterized by high prevalence and morbidity of HCV infection. Identification of HCV genotype and mutations associated with resistance to direct-acting antiviral (DAA) plays an important role either in conducting molecular epidemiological studies or choosing the treatment tactics. The aim of the work was to research of the genotype diversity of HCV variants circulating in Kyrgyzstan and the identification among them the mutations associated with the development of resistance to DAA. Materials and methods. 38 serum samples from HCV-infected residents of Kyrgyzstan were analyzed in this study. The nucleotide sequences of viral gene fragments (NS3, NS5A, NS5B) were determined by Sangers sequencing and deposited in the international GenBank database under the numbers ON841497ON841534 (NS5B), ON841535ON841566 (NS5A), and ON841567ON841584 (NS3). Results. The HCV subtypes 1b (52.6%; 95% CI 37.367.5%), 3a (44.8%; 95% CI 30.260.2%) and 1a (2.6%; 95% CI 0.513.4%) are circulating in Kyrgyzstan. 37% (95% CI 1959%) of subtype 1b isolates had C316N mutation in the NS5A gene; 46% (95% CI 2370%) had F37L mutation in the NS5A gene; 45% (95% CI 2272%) had Y56F mutation in the NS3 gene. Among subtype 3a isolates, resistance-associated mutations in NS5B fragment were not found. 22% (95% CI 945%) of subtype 3a sequences had a Y93H mutation in the NS5A gene. A combination of Y56F + Q168 + I170 mutations was identified among all sequences of NS3 gene. DAA resistance mutations were not found in NS3, NS5A, NS5B genes of subtype 1a sequence. Conclusion. A rather high prevalence of mutations associated with resistance or significant decrease in sensitivity to DAA among HCV sequences from Kyrgyzstan was shown. Updating of data on HCV genetic diversity is necessary for timely planning of measures to combat epidemic.