| Summary: | <p>Abstract</p> <p>Background</p> <p>HIV-1 derives from multiple independent transfers of simian immunodeficiency virus (SIV) strains from chimpanzees to human populations. We hypothesized that human populations in west central Africa may have been exposed to SIV prior to the pandemic, and that previous outbreaks may have selected for genetic resistance to immunodeficiency viruses. To test this hypothesis, we examined the genomes of Biaka Western Pygmies, who historically resided in communities within the geographic range of the central African chimpanzee subspecies (<it>Pan troglodytes troglodytes</it>) that carries strains of SIV ancestral to HIV-1.</p> <p>Results</p> <p>SNP genotypes of the Biaka were compared to those of African human populations who historically resided outside the range of <it>P. t. troglodytes</it>, including the Mbuti Eastern Pygmies. Genomic regions showing signatures of selection were compared to the genomic locations of genes reported to be associated with HIV infection or pathogenesis. In the Biaka, a strong signal of selection was detected at <it>CUL5</it>, which codes for a component of the vif-mediated APOBEC3 degradation pathway. A <it>CUL5</it> allele protective against AIDS progression was fixed in the Biaka. A signal of selection was detected at <it>TRIM5,</it> which codes for an HIV post-entry restriction factor. A protective mis-sense mutation in <it>TRIM5</it> had the highest frequency in Biaka compared to other African populations, as did a protective allele for <it>APOBEC3G</it>, which codes for an anti-HIV-1 restriction factor. Alleles protective against HIV-1 for <it>APOBEC3H</it>, <it>CXCR6</it> and <it>HLA-C</it> were at higher frequencies in the Biaka than in the Mbuti. Biaka genomes showed a strong signal of selection at <it>TSG101,</it> an inhibitor of HIV-1 viral budding.</p> <p>Conclusions</p> <p>We found protective alleles or evidence for selection in the Biaka at a number of genes associated with HIV-1 infection or progression. Pygmies have also been reported to carry genotypes protective against HIV-1 for the genes <it>CCR5</it> and <it>CCL3L1.</it> Our hypothesis that HIV-1 may have shaped the genomes of some human populations in West Central Africa appears to merit further investigation.</p>
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