To date, 11 HIV-1 subtypes and 48 circulating recombinant forms have been described worldwide. The underlying reason why their distribution is so heterogeneous is not clear. Host genetic factors could partly explain this distribution. The aim of this study was to describe HIV-1 strains circulating in an unexplored area of Mekong Delta, Vietnam, and to assess the impact of optimal epitope mutations on HLA binding.
We recruited 125 chronically antiretroviral-naive HIV-1-infected subjects from five cities in the Mekong Delta. We performed high-resolution DNA typing of HLA class I alleles, sequencing of Gag and RT-Prot genes and phylogenetic analysis of the strains. Epitope mutations were analyzed in patients bearing the HLA allele restricting the studied epitope. Optimal wild-type epitopes from the Los Alamos database were used as reference. T-cell epitope recognition was predicted using the immune epitope database tool according to three different scores involved in antigen processing (TAP and proteasome scores) and HLA binding (MHC score).
All sequences clustered with CRF01_AE. HLA class I genotyping showed the predominance of Asian alleles as A*11:01 and B*46:01 with a Vietnamese specificity held by two different haplotypes. The percentage of homology between Mekong and B consensus HIV-1 sequences was above 85%. Divergent epitopes had TAP and proteasome scores comparable with wild-type epitopes. MHC scores were significantly lower in divergent epitopes with a mean of 2.4 (±0.9) versus 2 (±0.7) in non-divergent ones (p<0.0001).
Our study confirms the wide predominance of CRF01_AE in the Mekong Delta where patients harbor a specific HLA pattern. Moreover, it demonstrates the lower MHC binding affinity among divergent epitopes. This weak immune pressure combined with a narrow genetic diversity favors immune escape and could explain why CRF01_AE is still predominant in Vietnam, particularly in the Mekong area.
Citation: Lazaro E, Thu Tram L, Bellecave P, Guidicelli G-L, Anies G, et al. (2011) Molecular Characterization of HIV-1 CRF01_AE in Mekong Delta, Vietnam, and Impact of T-Cell Epitope Mutations on HLA Recognition (ANRS 12159). PLoS ONE 6(10): e26244. doi:10.1371/journal.pone.0026244
Editor: Chiyu Zhang, Jiangsu University, China
Received: December 9, 2010; Accepted: September 23, 2011; Published: October 19, 2011
Copyright: © 2011 Lazaro et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This study was supported by Agence Nationale de Recherches Sur le sida et les hepatites virales (ANRS) (ANRS 12159). PB was supported by a fellowship from the European Community's Seventh Framework Program (FP7/2007–2013) under the “Collaborative HIV and Anti-HIV Drug Resistance Network” project (grant no. 223131). The funders had no role in study design, data collection, decision to publish or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
* E-mail: firstname.lastname@example.org
# These authors contributed equally to this work.
CLICK HERE FOR FULL-TEXT PDF