Molecular Epidemiology and Interferon Susceptibility of the Natural Recombinant Hepatitis C Virus Strain RF1_2k/1b

Background. Hepatitis C virus (HCV) genotype is an important determinant of virological response to antiviral therapies. Currently, there are no data available on the molecular epidemiology and interferon susceptibility of the natural intergenotypic recombinant RF1_2k/1b (RF1) strain. Methods. Genotyping and RF1-PCR screening were performed on samples from 604 HCVRNA-positive individuals from 7 countries. uPA/SCID mice carrying human hepatocytes (chimeric mice) were infected with the RF1_2k/1b strain, and the susceptibility of the strain to interferon and ribavirin was compared with the susceptibilities of 2 different strains of genotype B, used as references. Results. Six new RF1 cases were identified in this study; 5 (2%) of 281 in Russia and 1 (1%) of 90 in Uzbekistan. Phylogenetic analyses based on Core/E1 and NS5b indicated that all RF1 representatives share a common evolutionary ancestor. Infection with RF1 was established in chimeric mice. Reduction of RF1 viral load was observed in response to 3 injections of 3 mu g/kg pegylated-interferon alpha-2a alone or in combination with 50 mg/kg of ribavirin (0.5 or 1.4 log-copies/mL). Conclusions. All identified RF1-type strains appear to be introduced from a single source, suggesting that intergenotypic recombination in HCV is sporadic and not associated with cocirculation of different genotypes in a population. The RF1 strain in this study was responsive to interferon in vivo.