Muñoz de Rueda, P.;
Jiménez-Ruiz, S. M.;
Quiles, R.;
Pavón-Castillero, E. J.;
Muñoz-Gámez, J. A.;
Casado, J.;
Gila, A.;
Ruiz-Extremera, A.;
Salmerón, J.
The antigenic variability of HCV in viral HLA-Ag binding is related to the activation of the host immune response
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Media type:
E-Article
Title:
The antigenic variability of HCV in viral HLA-Ag binding is related to the activation of the host immune response
Contributor:
Muñoz de Rueda, P.;
Jiménez-Ruiz, S. M.;
Quiles, R.;
Pavón-Castillero, E. J.;
Muñoz-Gámez, J. A.;
Casado, J.;
Gila, A.;
Ruiz-Extremera, A.;
Salmerón, J.
imprint:
Springer Science and Business Media LLC, 2017
Description:
<jats:title>Abstract</jats:title><jats:p>Our previous data show that hepatitis C virus (HCV) genotype 1 patients expressing the HLA-DQB1 * 0301 allele have a combined response probability of 69%, while the remaining 31% do not respond, probably because the HCV immunodominant epitope (IE) against the DQB1 * 0301 allele is mutated. HCV IE (region sequenced in NS3 is a region encoding aa 1253–1272) from 37 patients (21 Sustained Virological Response, SVR; 16 non-SVR) HLA-DQB1 * 0301+, were analysed by pyrosequencing.<jats:italic>In vitro</jats:italic>cultures were also determined by CD4+ proliferation, using non-mutated IE (wild-type synthetic peptide) and synthetic mutated peptide. The pyrosequencing study revealed 34 different haplotypes. The SVR patients had fewer haplotypes (P = 0.07), mutations/haplotypes (P = 0.01) and polymorphic sites (P = 0.02) than non-SVR. Three polymorphic sites were associated with the non-SVR patients: haplotype 7 (L5P); haplotype 11 (L7P); and haplotype 15, (L15S) (P = 0.02). The<jats:italic>in vitro</jats:italic>study (n = 7) showed that in 4/7 patients (Group 1) the CD4+ proliferation obtained with wild-type synthetic peptide was higher than that obtained with the negative control and with the synthetic mutated peptide (P = 0.039). However, in the remaining 3/7 patients (Group 2) this pattern was not observed (P = 0.7). Our findings suggest that HLA-DQB1 * 0301+ patients with high antigenic variability in HCV IE (NS31253-1272) have a lower SVR rate, due to reduced CD4+ proliferation as a result of incorrect viral HLA-Ag binding.</jats:p>