"Characterizing the functional consequences of APOBEC3 polymorphism in African Green Monkeys"
I am studying the prevalence of Single Nucleotide Polymorphisms (SNPs) in primate antiviral genes. The Emerman lab has shown that host defense factors such as APOBEC3H exhibit population-specific SNPs that alter their antiviral activity. It is thought that these subtle differences between different versions (alleles) of antiviral genes may affect an individual's susceptibility to infections by viruses such as HIV-1. Furthermore, I suspect that different alleles of antiviral genes may exert differential selective pressure against invading viruses, driving evolution and adaptation to the host it has infected. It is unclear whether host defense factors, such as APOBEC3, are polymorphic in non-human primates, and whether this affects the evolution of SIV circulating in African primate populations.
I have chosen to examine this question by studying SIV infection in African Green Monkey (AGM) species. AGM is a superspecies consisting of 4 species that are geographically separated from one another throughout continental Africa. AGM are of great interest to retrovirologists because they are naturally infected with strains of Simian Immunodeficiency Virus (SIV). Chronic SIV infection in AGM (SIVagm) is asymptomatic and does not progress to simian AIDS, as opposed to the highly pathogenic HIV-1 pandemic in humans. Notably, SIVagm is comprised of four strains that infect AGM in a species-specific manner. This observation was thought to be exemplary of ancient host-virus coevolution. However, comprehensive phylogenetic analysis has revealed that SIVagm most likely swept across already-established AGM lineages just thousands of years ago. In this model, the driving forces behind SIVagm divergence into four distinct subtypes is unknown. In my research I am assessing whether different AGM species express different versions of host antiviral genes that may drive SIV along different evolutionary trajectories, resulting in divergence and species-specific host adaptation.
Contrary to my hypothesis, my preliminary results demonstrate that multiple APOBEC3H alleles are generated by a high degree of polymorphism, and that these alleles are shared among AGM species. Since the AGM species diverged around 2-3 million years ago, evidence of shared polymorphism in the APOBEC3H gene may suggest that the gene locus is undergoing balancing selection. I will use a battery of tools from population genetics to determine the likelihood of this scenario, and increase my sample size to include large numbers of all four AGM species.