title: Role of individual's T-cell immunome in controlling HIV-1 progression.
abstract: Viral and host factors can influence HIV-1 progression, among them human leucocyte antigen (HLA) has shown the strongest effect. However, studies on the functional contribution of HLA in controlling HIV progression toward AIDS are limited by multiple issues, including the viral strain variability within the study subjects. In this study, in a cohort of children infected with a monophyletic strain (CRF02_AG) during an outbreak, we evaluated the HIV-1 Gag, Vif, Vpr, Tat and hepatitis C virus E1/E2 (as control) proteins circulating in a cohort for the capability to be presented by the HLA molecules in the same population. A total of 70 Non-progressors and 37 Progressors to AIDS were evaluated. In the presence of a constant capability of HIV-1 to mutate in the region containing epitopes of Gag protein, the number of epitopes recognized in silico by the combination of the HLA alleles along the Gag consensus sequence is significantly higher in the Non-progressors compared with Progressors (HLA-A: Non-progressors = 1.532 ± 1.211, Progressors = 0.7714 ± 1.031, P = 0.0016; HLA-B: Non-progressors = 1.556 ± 1.298, Progressors = 1.000 ± 0.817, P = 0.0319; HLA-DR: Non-progressors = 13.30 ± 9.488, Progressors = 7.294 ± 6.952, P = 0.0006). Similar results were obtained for the other HIV-1 proteins Vif and Vpr, whereas no differences were obtained in the number of epitopes for the hepatitis C virus E1/E2 protein sequence or for the scrambled HIV-1 sequence. Finally, the results were confirmed also in a subgroup of subjects where both HLA typing and Gag sequence were available. In conclusion, in the absence of bias due to viral strain diversity, it is the overall fitting of the HLA molecules that are capable of better binding HIV-1 proteins in determining the major role in the control of HIV-1 replication and progression to AIDS.
authors: Department of Biology, University of Rome 'Tor Vergata', Rome, Italy.
authors: Alba
authors: A
authors: Grifoni
authors: Carla
authors: C
authors: Montesano
authors: Paolo
authors: P
authors: Palma
authors: Marta
authors: M
authors: Giovanetti
authors: Marta
authors: M
authors: Giovannetti
authors: Guido
authors: G
authors: Castelli-Gattinara
authors: Massimo
authors: M
authors: Ciccozzi
authors: Maurizio
authors: M
authors: Mattei
authors: Giorgio
authors: G
authors: Mancino
authors: Alfredo
authors: A
authors: Salerno
authors: Vittorio
authors: V
authors: Colizzi
authors: Massimo
authors: M
authors: Amicosante
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D016384:Consensus Sequence; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D010641:Phenotype; D010802:Phylogeny; D016415:Sequence Alignment; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D019562:Viral Load; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics
chemical_list: D006680:HLA Antigens; D054301:gag Gene Products, Human Immunodeficiency Virus
keywords: AIDS; MHC; antigens; epitopes; peptides; viral