title: On hepatitis C virus evolution: the interaction between virus and host towards treatment outcome.
abstract: BACKGROUND
  Hepatitis C is a disease spread throughout the world. Hepatitis C virus (HCV), the etiological agent of this disease, is a single-stranded positive RNA virus. Its genome encodes a single precursor protein that yields ten proteins after processing. NS5A, one of the non-structural viral proteins, is most associated with interferon-based therapy response, the approved treatment for hepatitis C in Brazil. HCV has a high mutation rate and therefore high variability, which may be important for evading the immune system and response to therapy. The aim of this study was to analyze the evolution of NS5A quasispecies before, during, and after treatment in patients infected with HCV genotype 3a who presented different therapy responses.
  
  
  METHODS
  Viral RNA was extracted, cDNA was synthesized, the NS5A region was amplified and cloned, and 15 clones from each time-point were sequenced. The sequences were analyzed for evolutionary history, genetic diversity and selection.
  
  
  RESULTS
  This analysis shows that the viral population that persists after treatment for most non-responder patients is present in before-treatment samples, suggesting it is adapted to evade treatment. In contrast, the population found in before treatment samples from most end-of-treatment responder patients either are selected out or appears in low frequency after relapse, therefore changing the population structure. The exceptions illustrate the uniqueness of the evolutionary process, and therefore the treatment resistance process, in each patient.
  
  
  CONCLUSIONS
  Although evolutionary behavior throughout treatment showed that each patient presented different population dynamics unrelated to therapy outcome, it seems that the viral population from non-responders that resists the treatment already had strains that could evade therapy before it started.
authors: Department of Biology, UNESP-São Paulo State University, IBILCE-Institute of Bioscience, Language & Literature and Exact Science, São José do Rio Preto, São Paulo, Brazil.
authors: Cíntia
authors: C
authors: Bittar
authors: Ana Carolina Gomes
authors: AC
authors: Jardim
authors: Lilian Hiromi Tomonari
authors: LH
authors: Yamasaki
authors: Claudia Márcia Aparecida
authors: CM
authors: Carareto
authors: João Renato Rebello
authors: JR
authors: Pinho
authors: Philippe
authors: P
authors: Lemey
authors: Isabel Maria Vicente Guedes
authors: IM
authors: de Carvalho-Mello
authors: Paula
authors: P
authors: Rahal
mesh_terms: D000595:Amino Acid Sequence; D019143:Evolution, Molecular; D014644:Genetic Variation; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006526:Hepatitis C / Q000628:therapy* / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D008969:Molecular Sequence Data; D016896:Treatment Outcome; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000378:metabolism; D012324:RNA-Dependent RNA Polymerase
chemical_list: D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
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