Variation in Chimp CD4 T Cells Helps Defend Against AIDS-Like Virus

Simian immunodeficiency virus (SIV), which infects chimpanzees and gorillas, has jumped the barrier from primates to humans on multiple occasions, one of which spawned the AIDS epidemic. Researchers studying the interaction of SIV and the primate CD4 T cells they infect have discovered a variation in these primates’ CD4 surface proteins that affects disease susceptibility and is not found in humans. Their study has been published in the Proceedings of the National Academy of Sciences.

The research was done by scientists at the University of Pennsylvania School of Medicine. Through characterization of fecal samples from over 500 chimpanzees across sub-Saharan Africa, the scientists discovered that these primates have over nine CD4 variants.

Analysis of these variants revealed that the mutations include amino acid changes in contact residues and glycans at the CD-4 envelope binding interface. These glycans clash with glycans on the SIV outer envelope, sterically hindering SIV’s entry into the cell. It had been previously established that primate CD4 evolved rapidly and these findings offer a plausible explanation as to why this is the case. Humans lack these protective glycans, leading the researchers to speculate as to whether this might be the reason for our relative susceptibility to SIV cross-species infection.

While SIV and HIV diverge significantly, previous studies have shown that the two share antibody cross-reactivity at the apex of their envelope spike. This conserved epitope could offer a potential target for vaccine development with combined HIV and SIV envelopes.

"Understanding how the diversification of the chimpanzee CD4 affects the structure and function of the chimpanzee SIV envelope has practical implications for AIDS vaccine development," says co-author George Shaw, MD, PhD, a professor of Medicine and Microbiology at Penn.

Image: A Gombe chimpanzee captures a juvenile red colobus monkey. Image courtesy of Ian C. Gilby.