Nonhuman Primate Genetics
Macaque monkeys are widely used in biomedical research. They also develop AIDS after infection with simian immunodeficiency virus (SIV), a virus that is nearly identical to HIV. Macaques are therefore the best animals for testing novel AIDS vaccine concepts and understanding AIDS pathogenesis. The severity of SIV infection varies among macaques, likely owing to genetic differences. A major research emphasis in our lab is understanding how macaque genetics influence susceptibility and resistance to infectious diseases, specifically SIV.
1) Major histocompatibility complex (MHC) genetics
The MHC consists of polymorphic genes that are important in the immune response to infectious diseases. Below are the genes of a normal individual, with the MHC region counterstained in red (and circled in yellow). Considering the size of this genetic region, its importance in determining individual susceptibility and resistance to disease is remarkable. On the right is a chart showing how much SIV virus is in the blood of macaques containing different MHC alleles. Notice how macaques with the alleles named ‘B*03/B*04’ have much lower amounts of SIV in their blood than macaques with ‘A*08’.
More than 1,000 MHC alleles have been described in humans. There are now nearly 500 known alleles in macaques, most of which have been described in the last two years. Our laboratory has described nearly 200 of these. We are continuing to characterize novel MHC alleles in rhesus, cynomolgus, and pig-tailed macaques.
We are also developing novel techniques to determine which MHC alleles are present in individual animals. Rapid genotyping is available only for the nine alleles shown in the figure above. Other alleles undoubtedly influence susceptibility SIV and other infectious diseases. Comprehensive genotyping will allow us to understand these associations.
2) Killer immunoglobulin receptor (KIR) genetics
Natural killer (NK) cells are important mediators of innate immunity. NK cell recognition of target cells is mediated through KIR genes, many of which interact with the MHC genes described above. Like MHC genes, KIR genes are highly variable. We are also just beginning to learn how KIR genes are organized in macaques. We recently described the organization of KIR genes in macaques.
Researchers have shown that specific combinations of MHC and KIR genes correlate with better control of HIV. We do not currently know which KIR genes interact with which MHC alleles in macaques. Characterizing these interactions is an ongoing topic of research in our lab.
Our nonhuman primate genetics research is funded by NIH NCRR and NIH NIAID.