Revista de SIDA e investigación clínica

Impact of Human Leukocyte Antigen Polymorphisms in Human Immunodeficiency Virus Progression in a Paediatric Cohort Infected with a Mono-phyletic Human Immunodeficiency Virus-1 Strain

Abstract

Carla Montesano, Cesira Tiziana Bonanno, Alba Grifoni, Caterina Di Sano, Paolo Palma, Guido Castelli-Gattinara, Maurizio Mattei, Giorgio Mancino, Alfredo Salerno, Vittorio Colizzi and Massimo Amicosante

Objective: HLA polymorphisms within the peptide binding pocket have been associated with rapid and slowprogression to AIDS, suggesting that the capability to present efficiently HIV-1 epitopes is crucial for the infection control. To minimize the effects of genetic background due to population coming from different geographic area and viral strain variability in the cohort, an analysis of all the polymorphisms associated with the HLA-A, -B and -DR alleles has been performed in a cohort of children with a monophyletic HIV-1 infection (CRF02_AG) during an outbreak in Libya.

Methods: High-resolution HLA-typing has been performed in 58 children infected with a monophyletic strain of HIV-1: 26 Long-Term Non-Progressors (LTNP), 9 Slow-Progressors (SP) and 23 Fast-Progressors (FP). HLA amino acid polymorphism frequency has been compared in the in FP respect to LTNP.

Results: HLA-B resulted the most interesting locus of the study; 10 positions located in B- and F-pocket for peptidebinding have been found significant after Bonferroni’s correction: 11S (LTNP=7.69% FP=34.78% OR=0.156 P<0.05), 74D (LTNP=15.38%, FP=52.17%, OR=0.167; p<0.015) and 94T (LTNP=15.38%, FP=52.17%, OR=0.045; p<0.001), resulted associated with AIDS progression; 66N (LTNP=42.31% FP=8.7% OR=7.7; p<0.02), 80I (LTNP=80.77%, FP=34.78%, OR=7.86; p<0.036), 81A (LTNP=84.61%, FP=47.83%, OR=6; p<0.015), 82L (LTNP=88.46%, FP=47.83%, OR=7.86; p<0.006) and 83R (LTNP=88.46%, FP=47.83%, OR=7.86; p<0.006), has been associated with non-progression. Further, carrying Bw4-epitope resulted associated with LTNP (phenotype-frequency: LTNP=88.46%, FP=47.83%, OR=8.36; p<0.006), with homozygosis for Bw4 (LTNP=30.8%, FP=8.7%, p<0.05) associated with delayed progression and homozygosis for Bw6 (LTNP=11.5%, FP=52.1%, p<0.05) associated with fast progression to AIDS.

Conclusion: The progression to AIDS might be in part determined by the binding capability of B-pocket and F-pocket of HLA-B and in part by the interaction of NK’s inhibitory receptor with HLA-B Bw4-epitope which regulate innate immune response and might have important implications for a better disease control.