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Association of hepatitis C virus NS5B variants with resistance to new antiviral drugs among untreated patients
Castilho, Magda Cristina Bernardino; Martins, Angélica Nascimento; Horbach, Ingrid Siciliano; Perez, Renata de Mello; Figueiredo, Fatima Aparecida Ferreira; Pinto, Paulo de Tarso Aparecida; Nabuco, Leticia Cancela; de Lima, Dirce Bonfim; Tanuri, Amílcar; Porto, Luis Cristóvão & Ferreira Júnior, Orlando da Costa
Abstract
Mutations located in the 109-amino acid fragment of NS5B are typically associated with resistance to interferon (IFN) and ribavirin (RIB) and to new antiviral drugs. The prevalence of these mutations was examined in 69 drug-naïve individuals with hepatitis C virus (HCV) infections in Rio de Janeiro, Brazil. Mutations related to non-response to IFN/RIB were observed in all subtypes studied (1a, 1b, 2b, 3a and 4). The most common mutation was Q309R, present in all subtypes, except subtype 2b with frequency above 20%. D244N was detected only in subtype 3a and A333E was detected only in subtype 2b. We did not detect the S282T, S326G or T329I mutations in any of the samples analysed. Of note, the C316N mutation, previously related to a new non-nucleoside compound (HCV796 and AG-021541), was observed in only eight of 33 (24%) samples from subtype 1b. Site 316 was under positive selection in this HCV variant. Our data highlight the presence of previously described resistance mutations in HCV genotypes from drug-naïve patients.
Keywords
HCV - NS5B - genotyping - Brazilian sequences - resistance mutation
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