title: Molecular characterization of HIV-1 CRF01_AE in Mekong Delta, Vietnam, and impact of T-cell epitope mutations on HLA recognition (ANRS 12159).
abstract: BACKGROUND
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors: Laboratoire de Virologie, CHU de Bordeaux et CNRS-UMR 5234, Université Victor Segalen-Bordeaux 2, Bordeaux, France.
authors: Estibaliz
authors: E
authors: Lazaro
authors: Luong Thu
authors: LT
authors: Tram
authors: Pantxika
authors: P
authors: Bellecave
authors: Gwenda-Line
authors: GL
authors: Guidicelli
authors: Guerric
authors: G
authors: Anies
authors: Huynh Hoang Khanh
authors: HH
authors: Thu
authors: Marie Pillot
authors: MP
authors: Debelleix
authors: Muriel
authors: M
authors: Vray
authors: Patricia
authors: P
authors: Recordon-Pinson
authors: Jean-Luc
authors: JL
authors: Taupin
authors: Truong Thi Xuan
authors: TT
authors: Lien
authors: Herve
authors: H
authors: Fleury
mesh_terms: D001483:Base Sequence; D017931:DNA Primers; D000939:Epitopes / Q000235:genetics*; D005787:Gene Frequency; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D009154:Mutation; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D014744:Vietnam
chemical_list: D017931:DNA Primers; D000939:Epitopes; D006680:HLA Antigens