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J Hepatol. 2010 Dec;53(6):1022-8. doi: 10.1016/j.jhep.2010.06.011. Epub 2010 Aug 3.

HLA class I allele associations with HCV genetic variants in patients with chronic HCV genotypes 1a or 1b infection.

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  • 1Klinikum der J.W. Goethe-Universit√§t Frankfurt am Main, Medizinische Klinik 1, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.



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.


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.


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.


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.

Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

[PubMed - indexed for MEDLINE]
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