Host Genetics of HIV-1 Susceptibility

Susceptibility to HIV-1 and the rate of disease progression reflect the influence of the genetic diversity of the virus as well as the variation in host factors. The virus will co-evolve with the host, escaping and adapting to host-determined influences. Dominant host factors currently identified include diversity in the major histocompatibility complex class I, and alleles of chemokine, chemokine receptor and cytokine genes. Recent work proposes new variants in life cycle genes and in antiviral innate defense, which modify HIV-1 susceptibility. Comparative genomics generates information on host cell barriers that may explain the current distribution of these viruses among human and nonhuman primates. A greater understanding of the genetic basis of human susceptibility to HIV-1 contributes to an understanding of the pathogenesis of the disease, helps identify new targets for prophylaxis and vaccine development and will lead to predictive tools to identify those at risk of rapid disease progression.