Genetic determinants of HIV‐1 infection and progression to AIDS: immune response genes

Abstract

Genomic studies involving well‐defined multicenter cohorts of HIV‐1/AIDS covering multiple populations have led to a greater understanding of the role of host determinants in viral acquisition, disease progression, transmission, and response to anti‐retroviral therapy. Similarly, recent knowledge on the virus genetic diversity has helped in elucidating mechanisms leading to the evolution of viral escape mutants and the role played by host immune determinants, in particular the major histocompatibility complex (MHC) associated genes. At least two alleles, HLA‐B*27 and B*57, have been identified as ‘protective’ against HIV‐1 while B*35 and B*53 act as susceptibility favoring factors. How human leukocyte antigen (HLA)‐mediated selection drives the evolution of HIV‐1 and which circulating variants are more likely to evade immune surveillance of the population are now beginning to become clear. Importantly, the rare HLA alleles in a population bear a selective advantage to the host because these can induce immune responses against pre‐adapted viruses. It is conceivable that previously established protective HLA associations are shifting with the evolving cytotoxic T lymphocyte (CTL) epitopes and may not remain protective in future. At the same time, this process is unraveling novel sub‐dominant epitopes of the virus which could now be incorporated as the dominant target CTL epitopes. An insight into the population‐specific correlates of protection is hence necessary for designing future anti‐HIV therapeutic and/or prophylactic vaccine formulation(s).

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

“…In agreement with previous observations, but with the limitation of the small study population studied, the data indicate that the ability of certain HLA peptide binding pockets to present a specific set of epitopes against which the subject can mount an immune response, might represent the basis of the susceptibility to AIDS progression, at least for the HLA-B locus [1,2,6,19].…”

“…Citation in controlling HIV infection [1,19]. As the T-cell response is dictated by HLA molecules, the individual's variation in the HLA class I and II alleles has a profound effect on the outcome of infection and disease progression to AIDS [2,19].…”

“…Susceptibility to HIV-1 infection, disease progression and clinical outcome are strongly influenced by differences observed in viral strains and host genetic factors [1].…”

“…However, the HLA association studies with HIV disease progression and outcome have been limiting by multiple issues such as: the involvement of multiple HLA loci, the linkage disequilibrium, the diploid genome, the cohort effects, the different measures of outcome and the viral strain variability within the study subjects [1,2]. might provide more relevant information on severity and diseases progression than the simply HLA allelic association.…”

“…Between a variety of genetic factors, certain specific alleles of human leukocyte antigen (HLA), both class I and II, have shown an effect on the outcome of HIV-1 infection, with many alleles found positively or negatively associated with disease progression to AIDS [1][2][3]. These findings are consistent with the role of HLA, particularly of class I molecules, in shaping the cell-mediated arm of anti-HIV immune response and in determining plasma viral load [4,5].…”