title: Influence of specific CD4+ T cells and antibodies on evolution of hypervariable region 1 during acute HCV infection.
abstract: OBJECTIVE
  Several studies suggest that the evolutionary rate of HVR1 sequence in acute HCV hepatitis derives from the action of a continuous immune-driven positive selection. However, these studies have not been performed examining the relationship between HVR1 evolution and the development of specific immunity to autologous HVR1 sequences.
  
  
  METHODS
  We performed a longitudinal analysis of HVR1 sequences and specific antibodies and CD4+ T cells in ten HCV acutely infected patients with different clinical outcomes (recovery versus persistence).
  
  
  RESULTS
  We showed that although both recovered and chronically evolving individuals developed IFN-gamma+ T cells specific for Core and NS sequences, HVR1-specific CD4+ T cells were detected only in patients clearing the virus. On the contrary, all patients displayed anti-HVR1 antibodies that recognized sequences exclusively carried by autologous viruses. Measurements of genetic diversity and the number of non-synonymous per synonymous substitutions within HVR1 sequences before and after antibody appearance showed an increase of these parameters only in concomitance with the appearance of anti-HVR1 antibodies.
  
  
  CONCLUSIONS
  The evidence that anti-HVR1 antibodies favor HVR1 variant selection suggests that viral complexity in chronically infected patients could represent a virus adaptive strategy to escape the continuous selective process mediated by anti-HVR1 antibodies.
authors.affiliation: Department of Cellular and Developmental Biology,"La Sapienza" University of Rome, Italy.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Scottà
authors.forename: Anna Rosa
authors.initials: AR
authors.lastname: Garbuglia
authors.forename: Lionello
authors.initials: L
authors.lastname: Ruggeri
authors.forename: Enea
authors.initials: E
authors.lastname: Spada
authors.forename: Luca
authors.initials: L
authors.lastname: Laurenti
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Perrone
authors.forename: Gabriella
authors.initials: G
authors.lastname: Girelli
authors.forename: Alfonso
authors.initials: A
authors.lastname: Mele
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Capobianchi
authors.forename: Antonella
authors.initials: A
authors.lastname: Folgori
authors.forename: Alfredo
authors.initials: A
authors.lastname: Nicosia
authors.forename: Paola
authors.initials: P
authors.lastname: Del Porto
authors.forename: Enza
authors.initials: E
authors.lastname: Piccolella
mesh_terms: D000208:Acute Disease; D000328:Adult; D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019143:Evolution, Molecular; D005260:Female; D014644:Genetic Variation; D006526:Hepatitis C / Q000276:immunology*; D018937:Hepatitis C Antibodies / Q000502:physiology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
chemical_list: C400562:HVR1 protein, Hepatitis C virus; D018937:Hepatitis C Antibodies; D014764:Viral Proteins