title: HLA class I allele associations with HCV genetic variants in patients with chronic HCV genotypes 1a or 1b infection.
abstract: OBJECTIVE
  The adaptive immune response against hepatitis C virus (HCV) is significantly shaped by the host's composition of HLA-alleles with the consequence that the HLA phenotype is a critical determinant of viral evolution during adaptive immune pressure. In the present study, we aimed to identify associations of HLA class I alleles with HCV subtypes 1a and 1b genetic variants.
  
  
  METHODS
  The association between HCV genetic variants and specific HLA-alleles was investigated in a cohort of 159 patients with chronic HCV genotypes 1a- and 1b-infection who were treated with pegylated interferon-alfa 2b and ribavirin in a prospective controlled trial for 48 weeks by direct sequencing of the genes encoding the HCV proteins E2, NS3, and NS5B and by HLA class I-genotyping of patients. HCV genetic variants were associated with specific HLA-alleles and the binding strength of accordant amino acid sequences to the corresponding HLA-allele was assessed by using the SYFPEITHI-algorithm.
  
  
  RESULTS
  Overall, associations between HLA class I alleles and HCV sequence variation were rare. Five unknown HLA class I-associated viral genetic variations were identified, which in part affected the binding of predicted HCV CD8+ T cell epitopes to the respective HLA-allele. In addition, different patterns of HLA class I-allele/HCV sequence associations between the two subtypes were observed.
  
  
  CONCLUSIONS
  We identified several unknown HLA class I-restricted HCV variants which in part impair binding to predicted HCV CD8+ T cell epitopes with remarkable differences between HCV subtypes 1a and 1b quasispecies.
authors.affiliation: Klinikum der J.W. Goethe-Universität Frankfurt am Main, Medizinische Klinik 1, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
authors.forename: Christian Markus
authors.initials: CM
authors.lastname: Lange
authors.forename: Kirsten
authors.initials: K
authors.lastname: Roomp
authors.forename: Anette
authors.initials: A
authors.lastname: Dragan
authors.forename: Jacob
authors.initials: J
authors.lastname: Nattermann
authors.forename: Monika
authors.initials: M
authors.lastname: Michalk
authors.forename: Ulrich
authors.initials: U
authors.lastname: Spengler
authors.forename: Viola
authors.initials: V
authors.lastname: Weich
authors.forename: Thomas
authors.initials: T
authors.lastname: Lengauer
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Thomas
authors.initials: T
authors.lastname: Berg
authors.forename: Christoph
authors.initials: C
authors.lastname: Sarrazin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D015331:Cohort Studies; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005805:Genes, MHC Class I; D056726:Genetic Association Studies; D014644:Genetic Variation; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics* / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000235:genetics / Q000276:immunology* / Q000821:virology*; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010802:Phylogeny; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D014759:Viral Envelope Proteins / Q000235:genetics; D017361:Viral Nonstructural Proteins / Q000235:genetics; D055815:Young Adult; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; D012324:RNA-Dependent RNA Polymerase
chemical_list: D017931:DNA Primers; D012367:RNA, Viral; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C091015:glycoprotein E2, Hepatitis C virus; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase