Novel association of five HLA alleles with HIV-1 progression in Spanish long-term non progressor patients

• Published in: PloS one 2019-08, Vol.14 (8), p.e0220459-e0220459
• Main Authors: Ramírez de Arellano, Eva, Díez-Fuertes, Francisco, Aguilar, Francisco, de la Torre Tarazona, Humberto Erick, Sánchez-Lara, Susana, Lao, Yolanda, Vicario, José Luis, García, Felipe, González-Garcia, Juan, Pulido, Federico, Gutierrez-Rodero, Félix, Moreno, Santiago, Iribarren, Jose Antonio, Viciana, Pompeyo, Vilches, Carlos, Ramos, Manuel, Capa, Laura, Alcamí, José, Del Val, Margarita
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; Acquired Immunodeficiency Syndrome - blood; Acquired Immunodeficiency Syndrome - genetics; Adolescent; Adult; Aged; AIDS; AIDS (Disease); AIDS patients; Alleles; Antigens; Biology and Life Sciences; CCR2 protein; Cytotoxicity; Development and progression; Disease Progression; Female; Gene frequency; Genes; Genetic analysis; Genetic aspects; Genetic diversity; Genetic factors; Genetic polymorphisms; Genetic variance; Genomes; Health aspects; Health care; Histocompatibility antigen HLA; HIV; HIV infections; HIV patients; HIV-1; HLA antigens; HLA Antigens - genetics; HLA Antigens - metabolism; Homozygosity; Hospitals; Human immunodeficiency virus; Humans; Immunology; Infections; Infectious diseases; Leukocytes; Lymphocytes; Male; Medicine and Health Sciences; Middle Aged; Monocyte chemoattractant protein 1; Nucleotides; People and Places; Phenotypes; Polymorphism, Single Nucleotide; Population; Population genetics; Population studies; Positive selection; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Spain; Studies; Viral Load
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0220459

Certain host genetic variants, especially in the human leucocyte antigen (HLA) region, are associated with different progression of HIV-1-induced diseases and AIDS. Long term non progressors (LTNP) represent only the 2% of infected patients but are especially relevant because of their efficient HIV control. In this work we present a global analysis of genetic data in the large national multicenter cohort of Spanish LTNP, which is compared with seronegative individuals and HIV-positive patients. We have analyzed whether several single-nucleotide polymorphisms (SNPs) including in key genes and certain HLA-A and B alleles could be associated with a specific HIV phenotype. A total of 846 individuals, 398 HIV-1-positive patients (213 typical progressors, 55 AIDS patients, and 130 LTNPs) and 448 HIV-negative controls, were genotyped for 15 polymorphisms and HLA-A and B alleles. Significant differences in the allele frequencies among the studied populations identified 16 LTNP-associated genetic factors, 5 of which were defined for the first time as related to LTNP phenotype: the protective effect of HLA-B39, and the detrimental impact of HLA-B18, -A24, -B08 and -A29. The remaining eleven polymorphisms confirmed previous publications, including the protective alleles HLA-B57, rs2395029 (HCP5), HLA bw4 homozygosity, HLA-B52, HLA-B27, CCR2 V64I, rs9264942 (HLA-C) and HLA-A03; and the risk allele HLA bw6 homozygosity. Notably, individual Spanish HIV-negative individuals had an average of 0.12 protective HLA alleles and SNPs, compared with an average of 1.43 protective alleles per LTNP patient, strongly suggesting positive selection of LTNP. Finally, stratification of LTNP according to viral load showed a proportional relationship between the frequency of protective alleles with control of viral load. Interestingly, no differences in the frequency of protection/risk polymorphisms were found between elite controllers and LTNPs maintaining viral loads