The Human Genes that Limit AIDS

The development of AIDS symptoms is a gradual process whereby a diverse population of HIV-1 genomes replicate in macrophages, monocytes, and T cells, challenging the immune system to its extreme. The cellular compartments and machinery that facilitate the process are human gene products that are punctuated by allelic variation that in some cases, determines the efficiency and kinetics of disease progression. Using molecular genetic typing of epidemiologic cohorts of HIV-1-infected study participants, we have searched for host genetic variants in genes whose products participate in HIV-1 replication. To date we have discovered attributable genetic influence on HIV-1 infection, disease progression, and AIDS sequelae involving coding and promoter regions of several human genes, namely CCR5, CCR2, SDF1, HLA-A, -B, and -C. This report will highlight the discovery, characterization and functioning of the multi-genic influences on the outcomes of HIV-1 infection and the influence of these variants on epidemiologic heterogeneity of the AIDS epidemic.