RT Journal Article
T1 The antigenic variability of HCV in viral HLA-Ag binding is related to the activation of the host immune response
A1 Munoz de Rueda, P.
A1 Jimenez-Ruiz, S. M.
A1 Quiles, R.
A1 Pavon-Castillero, E. J.
A1 Munoz-Gamez, J. A.
A1 Casado, J.
A1 Gila, A.
A1 Ruiz-Extremera, A.
A1 Salmeron, J.
K1 Hepatitis-c virus
K1 T-cell response
K1 Protease inhibitor
K1 Infection
K1 Interferon
K1 Resistance
K1 Mutations
K1 Ns3
K1 Sofosbuvir
K1 Clearance
AB 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. In vitro 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 in vitro 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.
PB Nature publishing group
SN 2045-2322
YR 2017
FD 2017-11-14
LK http://hdl.handle.net/10668/18906
UL http://hdl.handle.net/10668/18906
LA en
DS RISalud
RD Apr 18, 2025