Immunogenetic surveillance of HIV/AIDS

Evolutionary pressure by viruses is most likely responsible for the extraordinary allelic polymorphism of genes encoding class I human leukocyte antigens (HLA) and killer immunoglobulin-like receptors (KIR). Such genetic diversity has functional implications for the immune response to viruses and generates population-based variations in HLA class I allele frequencies and KIR gene profiles. The HIV-1 virus has relatively recently established itself as a major human pathogen, rapidly diversifying into a variety of phylogenetic subtypes or clades (A-G) and recombinants in different populations. HIV-1 clade C is the most common subtype in circulation accounting for 48% of all infections, followed by HIV-1 clades A and B which are responsible for 13% and 11% of infections in the current pandemic, respectively. Candidate gene studies of large cohorts of predominantly HIV-1 clade B but also clades C and A infected patients, have consistently shown significant associations between certain HLA class I alleles namely HLA-B*57, B*58, B*27, B*51 and relatively low viraemia. However, there is evidence that other associations between HLA-B*15, B*18 or B*53 and levels of HIV-1 viraemia are clade-specific. Recent genome-wide association studies of HIV-1 clade B exposed cohorts have confirmed that HLA-B, which is the most polymorphic locus in the human genome, is the major genetic locus contributing to immune control of viraemia. Moreover, the presence of natural killer cell receptors encoded by KIR-3DL1 and 3DS1 genes together with certain HLA class I alleles carrying the KIR target motif Bw4Ile80, provides an enhanced ability to control HIV-1 viraemia in some individuals. It is likely that rapid co-evolution of HIV-1 immune escape variants together with an adjustment of human immune response gene profiles has occurred in some exposed populations. Taken together, immunogenetic surveillance of HIV-1 exposed cohorts has revealed important correlates of natural immunity, which could provide a rational platform for the design and testing of future vaccines aimed at controlling the current AIDS pandemic.