AIDS-protective HLA-B*27/B*57 and chimpanzee MHC class I molecules target analogous conserved areas of HIV-1/SIV_cpz

Abstract

In the absence of treatment, most HIV-1-infected humans develop AIDS. However, a minority are long-term nonprogressors, and resistance is associated with the presence of particular HLA-B*27/B*57 molecules. In contrast, most HIV-1-infected chimpanzees do not contract AIDS. In comparison with humans, chimpanzees experienced an ancient selective sweep affecting the MHC class I repertoire. We have determined the peptide-binding properties of frequent chimpanzee MHC class I molecules, and show that, like HLA-B*27/B*57, they target similar conserved areas of HIV-1/SIV cpz . In addition, many animals appear to possess multiple molecules targeting various conserved areas of the HIV-1/SIV cpz Gag protein, a quantitative aspect of the immune response that may further minimize the chance of viral escape. The functional characteristics of the contemporary chimpanzee MHC repertoire suggest that the selective sweep was caused by a lentiviral pandemic.

HLA-B*44 Is Associated with a Lower Viral Set Point and Slow CD4 Decline in a Cohort of Chinese Homosexual Men Acutely Infected with HIV-1

“…This will allow physicians to control viremia in different parts of the world. Only two variants, HLA-B*27 and -B*57, have consistently been associated with lower viral load and better clinical outcomes (7)(8)(9)(10). However, the effects of individual HLA alleles, haplotypes, and supertypes with reported impacts on HIV-1 viral load are not always clear because their distributions and patterns of linkage disequilibrium often differ from one population to another (11,12).…”

Host Genes Important to HIV Replication and Evolution

“…Chimpanzees can be infected with HIV-1; however, most do not develop AIDS. The contemporary MHC class I repertoire of chimpanzees targets analogous conserved domains of HIV-1/SIV cpz to those targeted by human protective alleles HLA-B Ã 57 and B Ã 27, in particular, of the Gag protein (de Groot et al 2010). The functional characteristics of the chimpanzee MCH-repertoire may be the result of a selective sweep caused by lentiviruses (de Groot et al 2010).…”

“…The contemporary MHC class I repertoire of chimpanzees targets analogous conserved domains of HIV-1/SIV cpz to those targeted by human protective alleles HLA-B Ã 57 and B Ã 27, in particular, of the Gag protein (de Groot et al 2010). The functional characteristics of the chimpanzee MCH-repertoire may be the result of a selective sweep caused by lentiviruses (de Groot et al 2010). The consistent identification of HLA-B Ã 57, HLA-B Ã 27, and HLA-B Ã 51 in host genome studies is attributed to fitness cost of mutating in the targeted viral epitopes and to the patterns of viral escape from CD8 þ T-cell recognition.…”

Bonobos Maintain Immune System Diversity with Three Functional Types of MHC-B

“…One population comprises the 125 wild Pts chimpanzees of Gombe National Park Tanzania (32). The other comprises 32 wild born Ptv chimpanzees from Sierra Leone that were used to found the captive population formerly housed at the Biomedical Primate Research Center (BPRC) in the Netherlands (31). HLA-B allele frequencies for six human populations were included in the comparisons.…”