title: Amino Acid Polymorphisms Within the Entire HCV NS5A Region in Estonian Chronic HCV 1b Patients With Different Treatment Response.
abstract: BACKGROUND
  A substantial proportion of hepatitis C virus (HCV)-1b infected patients do not response to pegylated interferon-α plus ribavirin (PegIFNα/RBV) combination therapy that was partially associated with mutations in the non-structural 5A (NS5A) protein.
  
  
  OBJECTIVE
  Analysis of NS5A polymorphisms in HCV genotype 1b pre-treatment serum samples from Estonian patients and their effect on the treatment response.
  
  
  METHODS
  Twenty-nine complete NS5A sequences obtained from patients with chronic HCV-1b infection who had received combined therapy with PegIFNα-2a/RBV were analyzed and compared with the prototype strain HCV-J. Twelve patients achieved a sustained virological response (SVR), 15 were non-SVR and 2 patients stopped treatment because of side effects.
  
  
  RESULTS
  No significant difference in total number of amino acid mutations was observed between isolates from SVR and non-SVR patients in any known regions of the NS5A protein. However, specific amino acid substitutions at positions 1989 and 2283 correlated significantly with SVR, mutations at positions 1979, 2107, 2171 and 2382 were associated with non-response to treatment and amino acid substitution at position 2319 was observed in relapsers. At phylogenetic analysis, NS5A nucleotide sequences have been subdivided into four groups characterized by the different treatment response. Twenty-four novel nucleotide polymorphisms and 11 novel amino acid polymorphisms were identified based on the phylogenetic tree topology.
  
  
  CONCLUSIONS
  Specific amino acid substitutions correlating with the treatment response were found. Polymorphisms revealed by phylogenetic analysis may define the signature patterns for treatment susceptible and treatment resistant strains prevalent in Estonia.
authors.affiliation: Department of Virology, National Institute for Health Development, Tallinn, Estonia.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Kuznetsova
authors.affiliation: Department of Virology, National Institute for Health Development, Tallinn, Estonia ; Department of Diagnostics and Vaccine, Unit for Molecular Typing, Swedish Institute for Communicable Disease Control, Stockholm, Sweden.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Tallo
authors.affiliation: Department of Internal Medicine, West-Tallinn Central Hospital, Tallinn, Estonia.
authors.forename: Vadim
authors.initials: V
authors.lastname: Brjalin
authors.affiliation: Department of Virology, National Institute for Health Development, Tallinn, Estonia.
authors.forename: Irina
authors.initials: I
authors.lastname: Reshetnjak
authors.affiliation: Department of Internal Medicine, University of Tartu, Tartu, Estonia.
authors.forename: Riina
authors.initials: R
authors.lastname: Salupere
authors.affiliation: Department of Virology, National Institute for Health Development, Tallinn, Estonia.
authors.forename: Ljudmilla
authors.initials: L
authors.lastname: Priimagi
authors.affiliation: Department of Virology, National Institute for Health Development, Tallinn, Estonia.
authors.forename: Olga
authors.initials: O
authors.lastname: Katargina
authors.affiliation: Department of Hemorrhagic Fevers and Pilot Projects, Federal State Budgetary Institution "Chumakov Institute of Poliomyelitis and Viral Encephalitides" of RAMS, Moscow, Russia.
authors.forename: Maria
authors.initials: M
authors.lastname: Smirnova
authors.affiliation: Protein Engineering Department, Latvian Biomedical Research and Study Centre, Riga, Latvia.
authors.forename: Juris
authors.initials: J
authors.lastname: Jansons
authors.affiliation: Department of Virology, National Institute for Health Development, Tallinn, Estonia.
authors.forename: Valentina
authors.initials: V
authors.lastname: Tefanova
keywords: Estonia; Hepatitis C; Ribavirin; Therapy