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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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Comparison of Gag (A) and RT (B) Vietnamese consensus sequences with HxB2 strains.Optimal CTL epitopes are highlighted by boxes. HLA restriction is indicated on the corresponding epitopes. Amino acid substitutions are indicated in bold. Shaded vertical bars separate blocks of 10 amino acids.
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pone-0026244-g003: Comparison of Gag (A) and RT (B) Vietnamese consensus sequences with HxB2 strains.Optimal CTL epitopes are highlighted by boxes. HLA restriction is indicated on the corresponding epitopes. Amino acid substitutions are indicated in bold. Shaded vertical bars separate blocks of 10 amino acids.

Mentions: Using this consensus sequence, we focused our analysis on polymorphisms present in optimal CTL epitopes as defined in the Los Alamos database. Figure 3 depicts the location and HLA restriction elements of CTL epitopes on Gag and RT sequences on HxB2 aligned with the CRF01_AE Vietnamese consensus sequence. As there are only very few differences between Mekong and whole CRF01_AE consensus sequences and these differences are not relevant in terms of HLA binding predictions, the consensus amino acid of CRF01_AE was not added in the figure.


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)

Comparison of Gag (A) and RT (B) Vietnamese consensus sequences with HxB2 strains.Optimal CTL epitopes are highlighted by boxes. HLA restriction is indicated on the corresponding epitopes. Amino acid substitutions are indicated in bold. Shaded vertical bars separate blocks of 10 amino acids.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0026244-g003: Comparison of Gag (A) and RT (B) Vietnamese consensus sequences with HxB2 strains.Optimal CTL epitopes are highlighted by boxes. HLA restriction is indicated on the corresponding epitopes. Amino acid substitutions are indicated in bold. Shaded vertical bars separate blocks of 10 amino acids.
Mentions: Using this consensus sequence, we focused our analysis on polymorphisms present in optimal CTL epitopes as defined in the Los Alamos database. Figure 3 depicts the location and HLA restriction elements of CTL epitopes on Gag and RT sequences on HxB2 aligned with the CRF01_AE Vietnamese consensus sequence. As there are only very few differences between Mekong and whole CRF01_AE consensus sequences and these differences are not relevant in terms of HLA binding predictions, the consensus amino acid of CRF01_AE was not added in the figure.

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