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
Carla Montesano1, Cesira Tiziana Bonanno2, Alba Grifoni1, Caterina Di Sano3, Paolo Palma5, Guido Castelli-Gattinara5, Maurizio Mattei6, Giorgio Mancino7, Alfredo Salerno2, Vittorio Colizzi1 and Massimo Amicosante4,8*
- *Corresponding Author:
- Massimo Amicosante
Department of Biomedicine and Prevention
University of Rome, Tor Vergata
Via Montpellier 100133, Rome, Italy
Tel: +39-06-7259 6202
Fax: +39-06-7259 6202
E-mail: [email protected]
Received Date: December 21, 2013; Accepted Date: January 29, 2014; Published Date: February 11, 2014
Citation: Montesano C, Bonanno CT, Grifoni A, Di Sano C, Palma P, et al. (2014) 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. J AIDS Clin Res 5:282. doi: 10.4172/2155-6113.1000282
Copyright: © 2014 Montesano C, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.