Parallel adaptation of CD4 in SIV-endemic Gorilla and Pan lineages

The simian immunodeficiency virus (SIV) is homologous to the human immunodeficiency virus (HIV), and naturally infects chimpanzees and gorillas in the wild. Some African primate species appear to have evolved resistance to SIV, in that the virus no longer is found in the species or, if infected, individuals within the species show no serious symptoms of simian AIDS (SAIDS). In contrast, Asian primate species do not appear to naturally harbor SIV and, like humans, often progress to AIDS following infection. CD4 is the primary T cell receptor that SIV/HIV interacts with to infect host T cells. Domain 1 (D1) of CD4 holds the main interaction with the viral envelope protein, gp120. During my course in Dr. Stewart’s lab, I analyzed 77 primate CD4 gene sequences in comparison to each other and to the Homo lineage in search of fixed changes on lineages, as well as sequence variation within species. I found that D1 in the known SIV resistant species, chimpanzee and gorilla, had several notable amino acid replacements on ancestral lineages, as well as variation within the species. These amino acid replacements likely have the potential to prevent SIV gp120 from binding to CD4. In contrast, the Homo sequence had no amino acid replacements and little variation within humans. Perhaps these results shed light on why humans suffer with HIV/AIDS today, with little to no resistance to infection.