Genetic subspecies diversity of the chimpanzee CD4 virus-receptor gene

Abstract

Chimpanzees are naturally and asymptomatically infected by simian immunodeficiency virus (SIV). Pathogenic properties of SIV/HIV vary and differences in susceptibility and pathogenicity of SIV/HIV depend in part on host-specific factors such as virus-receptor/co-receptor interactions. Since CD4 plays a primary role in virus binding and since SIVcpz have been found only in two African chimpanzee subspecies, we characterized the genetic diversity of CD4 receptors in all four recognized subspecies of chimpanzees. We found noticeable variation in the first variable region V1 of CD4 and in intron six among the subspecies of chimpanzees. We found the CD4 receptor to be conserved in individuals belonging to the P. t. verus subspecies and divergent from the other three subspecies, which harbored highly variable CD4 receptors. The CD4 receptor of chimpanzees differed from that of humans. We question whether the observed diversity can explain the species-specific differences in susceptibility to and pathogenicity of SIV/HIV.

A glycan shield on chimpanzee CD4 protects against infection by primate lentiviruses (HIV/SIV)

“…This resulted in 24 CD4 sequences, never before reported, covering all four chimpanzee subspecies. In addition, we obtained CD4 genotype data from a previous study on chimpanzee CD4 (33), and also sequenced CD4 from four additional individuals ourselves [P.t. troglodytes (n = 1), P.t.…”

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

“…Although heterozygous advantage may have an additional impact, other host and viral factors may play a role as well. In this respect, it is worth mentioning that we do not want to claim that the MHC is the only genetic region that explains the relative resistance to AIDS in chimpanzees, because other genes, such as the chemokine (C-C motif) receptor 5 and CD4, show signs of selection and may have been affected by a sweep as well (34,35). Furthermore, it was shown recently that rhesus macaques that are elite controllers in AIDS vaccine studies possess T-cell responses to different viral proteins, primarily Vif and Nef, restricted by the Mamu-B*08 or -B*17 molecule (36,37).…”

“…Nonhuman primate species have been challenged by SIV infections over long periods of time, and must have developed ways to control the development of AIDS (15, 40), like the AIDS-resistant West African chimpanzees studied here. There is evidence that the selective sweep or subsequent selection processes must have been more prominent in West African chimpanzees than in other chimpanzee populations (34,35,41). This may be due to population separation, and may be dependent on the monkey species being preyed upon and on their respective SIV infections (42).…”

The HIV-1 pandemic: does the selective sweep in chimpanzees mirror humankind’s future?

“…There is evidence that the selective sweep or subsequent selection processes must have been more prominent in West-African chimpanzees than in other chimpanzee populations [96,97,114]. Population separation may have influenced this.…”