title: Genetic variability of hepatitis C virus NS3 protein in human leukocyte antigen-A2 liver transplant recipients with recurrent hepatitis C.
abstract: The association between the severity of chronic hepatitis C and the variability of the hepatitis C virus (HCV) genome remains controversial, but to our knowledge few data are available to date regarding T-cell epitope coding regions in transplant patients. In the current study, we identified 21 human leukocyte antigen (HLA)-A2-positive Spanish patients with chronic hepatitis C, 14 immunosuppressed liver transplant recipients, and 7 immunocompetent controls. Alanine aminotransferase, aspartate aminotransferase, viral load, and rate of fibrosis progression were determined. Genetic distances of HCV isolates and variations in epitopes of the HCV nonstructural 3 protein (NS3-1393 LIFCHSKKK and NS3-1406 KLVALGINAV) were compared between patients with slow or fast progression of fibrosis. Isolates from transplant patients with fast progression were found to be more divergent (P =.03), had a higher mean value of synonymous (dS) variations (P =.02), and some were differentiated in a phylogenetic tree, compared with isolates from patients with slow progression. The HLA-A2-restricted NS3-1406 epitope was found to be more variable (20 of 21 isolates differed from the prototype) compared with the A3-restricted NS3-1392 epitope (19% vs. 1.25% variation). A shift in the viral peptide was not detected in a subset of transplant patients, but was evident in two of three nontransplant patients with follow-up. There was no correlation noted between a particular amino acid variation and fibrosis progression (slow or fast) in either transplant or nontransplant patients. The results of the current study suggest that 1) there may be different HCV-1b strains in our geographic area, 2) immunosuppression appears to have little effect in amino acid variation at the HCV NS3-1406 epitope, and 3) variations over time might be more frequent in nonimmunosuppressed patients.
authors.affiliation: Microbiology, Hospital Universitari La Fe and Centro de Investigación, Valencia, Spain. fxlopez@teleline.es
authors.forename: F Xavier
authors.initials: FX
authors.lastname: López-Labrador
authors.forename: Marina
authors.initials: M
authors.lastname: Berenguer
authors.forename: Amparo
authors.initials: A
authors.lastname: Sempere
authors.forename: Martín
authors.initials: M
authors.lastname: Prieto
authors.forename: Rafael
authors.initials: R
authors.lastname: Sirera
authors.forename: Andrés
authors.initials: A
authors.lastname: González-Molina
authors.forename: Vicente
authors.initials: V
authors.lastname: Ortiz
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Marty
authors.forename: Joaquín
authors.initials: J
authors.lastname: Berenguer
authors.forename: Miguel
authors.initials: M
authors.lastname: Gobernado
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001483:Base Sequence; D005260:Female; D014644:Genetic Variation; D015789:HLA-A2 Antigen / Q000032:analysis*; D006526:Hepatitis C; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010802:Phylogeny; D012008:Recurrence; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D015789:HLA-A2 Antigen; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases