title: Association of hepatitis C virus NS5B variants with resistance to new antiviral drugs among untreated patients.
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.
authors.affiliation: Laboratório de Histocompatibilidade e Criopreservação, Policlínica Piquet Carneiro, Departamento de Histologia e Embriologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil. magdacastilho@yahoo.com.br
authors.forename: Magda Cristina Bernardino
authors.initials: MC
authors.lastname: Castilho
authors.forename: Angélica Nascimento
authors.initials: AN
authors.lastname: Martins
authors.forename: Ingrid Siciliano
authors.initials: IS
authors.lastname: Horbach
authors.forename: Renata de Mello
authors.initials: Rde M
authors.lastname: Perez
authors.forename: Fatima Aparecida Ferreira
authors.initials: FA
authors.lastname: Figueiredo
authors.forename: Paulo de Tarso Aparecida
authors.initials: Pde T
authors.lastname: Pinto
authors.forename: Leticia Cancela
authors.initials: LC
authors.lastname: Nabuco
authors.forename: Dirce Bonfim de
authors.initials: DB
authors.lastname: Lima
authors.forename: Amílcar
authors.initials: A
authors.lastname: Tanuri
authors.forename: Luis Cristóvão
authors.initials: LC
authors.lastname: Porto
authors.forename: Orlando da Costa
authors.initials: Oda C
authors.lastname: Ferreira Júnior
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics*; D006526:Hepatitis C / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D007372:Interferons / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D012254:Ribavirin / Q000494:pharmacology* / Q000627:therapeutic use; D016415:Sequence Alignment; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D007372:Interferons; D012254:Ribavirin; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase