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Molecular characterization of HIV-1 CRF01_AE in Mekong Delta, Vietnam, and impact of T-cell epitope mutations on HLA recognition (ANRS 12159).

Lazaro E, Tram LT, Bellecave P, Guidicelli GL, Anies G, Thu HH, Debelleix MP, Vray M, Recordon-Pinson P, Taupin JL, Lien TT, Fleury H - PLoS ONE (2011)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire de Virologie, CHU de Bordeaux et CNRS-UMR 5234, Université Victor Segalen-Bordeaux 2, Bordeaux, France.

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.

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HLA allele frequencies in the Vietnamese Mekong Delta population (n = 116) compared to Kinh Vietnamese (dashed bars), Chinese (grey bars) and European (white bars) populations.The 6 most representative HLA alleles of the Mekong Delta population are represented.
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pone-0026244-g004: HLA allele frequencies in the Vietnamese Mekong Delta population (n = 116) compared to Kinh Vietnamese (dashed bars), Chinese (grey bars) and European (white bars) populations.The 6 most representative HLA alleles of the Mekong Delta population are represented.

Mentions: HLA class I typing was performed for 116 patients. The number of different HLA-A, HLA-B and HLA-Cw alleles detected in this study was 21, 42 and 21 respectively. The five most frequent HLA class I alleles in the Mekong population are represented in Figure 4 and are compared to three other populations: Vietnamese, Chinese and Caucasian people.


Molecular characterization of HIV-1 CRF01_AE in Mekong Delta, Vietnam, and impact of T-cell epitope mutations on HLA recognition (ANRS 12159).

Lazaro E, Tram LT, Bellecave P, Guidicelli GL, Anies G, Thu HH, Debelleix MP, Vray M, Recordon-Pinson P, Taupin JL, Lien TT, Fleury H - PLoS ONE (2011)

HLA allele frequencies in the Vietnamese Mekong Delta population (n = 116) compared to Kinh Vietnamese (dashed bars), Chinese (grey bars) and European (white bars) populations.The 6 most representative HLA alleles of the Mekong Delta population are represented.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3198469&req=5

pone-0026244-g004: HLA allele frequencies in the Vietnamese Mekong Delta population (n = 116) compared to Kinh Vietnamese (dashed bars), Chinese (grey bars) and European (white bars) populations.The 6 most representative HLA alleles of the Mekong Delta population are represented.
Mentions: HLA class I typing was performed for 116 patients. The number of different HLA-A, HLA-B and HLA-Cw alleles detected in this study was 21, 42 and 21 respectively. The five most frequent HLA class I alleles in the Mekong population are represented in Figure 4 and are compared to three other populations: Vietnamese, Chinese and Caucasian people.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire de Virologie, CHU de Bordeaux et CNRS-UMR 5234, Université Victor Segalen-Bordeaux 2, Bordeaux, France.

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.

Show MeSH