Certain pathogens, including viruses, appear to utilize the alpha1-3GT gene, its enzymatic pathway, or its product gal-alpha1-3Gal in their infection cycles. This study investigates how the alpha1-3GT gene and its product, gal-alpha1-3Gal (present on host cells), affect viral infectivity in primates. Among mammals, catarrhines (Old World monkeys and apes) are the only ones that do not express the alpha1-3GT gene which was inactivated ~28 million years ago. If it can be established that these pathogens do indeed use the gene, its enzymatic pathway, or its product, in their infection cycles, then the selective advantage of this gene inactivation becomes clear. To test this possibility, experiments will probe the mechanisms by which viruses can (or cannot) utilize the gene or gene product. In vitro experiments on parallel mouse and primate cell lines, genetically modified to express the alpha1-3GT gene, will test the differential infectivity of viruses. Additionally, genetically modified mouse lines, one expressing the alpha1-3GT gene and the other with the gene "knockedout" will be used to corroborate in vitro work and to test pathogenesis. This research elucidates how different viruses use glycosylation pathways or carbohydrates as binding sites or receptors. This has biomedical implications by contributing to understanding how the immune system responses to infection. It also elucidates variation in viral virulence in catarrhines and other species including its contribution to selective pressures and species survival. The broader impacts of this study include primate conservation, as conservation biologists are increasingly aware of the threat of emerging diseases in primate communities. Understanding which viruses are likely to be most dangerous to particular hosts may be critical in making informed policy decisions. This doctoral dissertation research project will contribute to the academic training of a female graduate student who is a member of the American Hispanic community. This research will broaden her ability to contribute to the growing discipline of global disease ecology.
