Reference : HLA class I allele associations with HCV genetic variants in patients with chronic HC...
Scientific journals : Article
Life sciences : Multidisciplinary, general & others
http://hdl.handle.net/10993/26992
HLA class I allele associations with HCV genetic variants in patients with chronic HCV genotypes 1a or 1b infection
English
Lange, Christian Markus [> >]
Roomp, Kirsten mailto [Max-Planck-Institut für Informatik]
Dragan, Anette [> >]
Nattermann, Jacob [> >]
Michalk, Monika [> >]
Spengler, Ulrich [> >]
Weich, Viola [> >]
Lengauer, Thomas [> >]
Zeuzem, Stefan [> >]
Berg, Thomas [> >]
Sarrazin, Christoph [> >]
2010
Journal of Hepatology
Elsevier
53
6
1022-1028
Yes (verified by ORBilu)
0168-8278
Oxford
United Kingdom
[en] Hepatitis C ; Genetic variants ; HLA-restricted epitopes ; Epitopes ; Immune pressure
[en] BACKGROUND & AIMS: 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.
http://hdl.handle.net/10993/26992
10.1016/j.jhep.2010.06.011

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