Influence of host genes on HIV-1 disease progression

The role of host genes in the course of HIV-1 infection has been examined in different populations and among all major risk groups. Two extended human lymphocyte antigen (HLA) haplotypes, HLA A1-Cw7-B8-DR3-DQ2 and HLA A11-Cw4-B35-DR1-DQ1, are found to be associated with a faster progression to AIDS. The complement C4 factor and tumor necrosis factor genes of the major histocompatibility complex, as well as the mannose binding protein gene, have also been suggested to influence the outcome of AIDS. The recent discovery that chemokine receptors could serve as cofactors for HIV-1 cell entry has prompted a search for polymorphisms in chemokine receptor genes. A 32 base pair inactivating deletion in the CCR5 gene and a point mutation within the CCR2b gene resulting in a conservative amino acid substitution have been examined and shown to be independently associated with delayed disease progression. Together, these observations strongly support a genetic component in AIDS pathogenesis. This article synthesizes the current state of knowledge about the influence of host genes on HIV-1 disease progression. It provides a summary of all significant association studies reported so far. The role of the allelic polymorphism in these genes is discussed with regard to the immunopathogenesis of AIDS.