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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.

Show MeSH
Comparisons of proteasome, TAP and MHC scores between wild-type (B sub-type) and divergent epitopes (CRF01_AE sequences).All scores are logarithmic values, high values corresponding to highly predicted efficiency.
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pone-0026244-g005: Comparisons of proteasome, TAP and MHC scores between wild-type (B sub-type) and divergent epitopes (CRF01_AE sequences).All scores are logarithmic values, high values corresponding to highly predicted efficiency.

Mentions: We then investigated amino acid divergences observed within CTL epitopes in the 105 Vietnamese RT-Prot and Gag sequences according to each individual's HLA restriction elements. We found 50 epitopes of interest presenting one to three divergences. The processing into the cell as well as the binding to HLA molecules of each divergent CTL epitope described in the Vietnamese sequences was predicted through the proteasome, TAP and MHC scores (Figure 5). The scores for the divergent epitopes were matched and compared with those obtained with the CTL epitopes described for subtype B. The analysis was performed extensively for each HLA restriction element whenever the HLA allele was available on the immune epitope database.


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)

Comparisons of proteasome, TAP and MHC scores between wild-type (B sub-type) and divergent epitopes (CRF01_AE sequences).All scores are logarithmic values, high values corresponding to highly predicted efficiency.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0026244-g005: Comparisons of proteasome, TAP and MHC scores between wild-type (B sub-type) and divergent epitopes (CRF01_AE sequences).All scores are logarithmic values, high values corresponding to highly predicted efficiency.
Mentions: We then investigated amino acid divergences observed within CTL epitopes in the 105 Vietnamese RT-Prot and Gag sequences according to each individual's HLA restriction elements. We found 50 epitopes of interest presenting one to three divergences. The processing into the cell as well as the binding to HLA molecules of each divergent CTL epitope described in the Vietnamese sequences was predicted through the proteasome, TAP and MHC scores (Figure 5). The scores for the divergent epitopes were matched and compared with those obtained with the CTL epitopes described for subtype B. The analysis was performed extensively for each HLA restriction element whenever the HLA allele was available on the immune epitope database.

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