Investigating an adaptive explanation for nonprogressor immune responses to SIV
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Date
2015-06
Authors
McVeety, Kelsie
Journal Title
Journal ISSN
Volume Title
Publisher
University of Oregon
Abstract
HIV/AIDS continues to be a widespread epidemic that is currently treated with immunotherapies that target the viral mechanisms, leaving room for the evolution of resistant strains. Most research into novel therapies that target the human immune response investigates the mechanisms that leave humans vulnerable to HIV infection. However, there is much to be gained by examining nonhuman primate species whose immune systems can naturally survive with high levels of replication of a related lentivirus, simian immunodeficiency virus (SIV), without the result of chronic immune activation or viral resistance. These species are known as nonprogressors, and by investigating an adaptive explanation for their tolerance of SIV this project sought to connect the evolutionary history of these species to variation in immune response to SIV, with the intent of identifying target genes and molecular pathways for future medical intervention and deepening our knowledge of how natural selection and coevolution with lentiviruses has shaped primate immune responses in general. Evolutionary genetic methods were used to test for positive selection, convergent evolution, and variants that distinguish nonprogressors from progressors in the protein-coding and cis-regulatory regions of four genes (CASP1, CD38, EEF1D, and SOCS1) differentially expressed in progressors and nonprogressors during the chronic phase of infection (Bosinger et. al. 2009). Results indicate these genes are largely conserved in these primates and have experienced negative selection. Furthermore, nonprogressors do not share derived variants in the promoter regions. Future research should look to test the functional significance of distinguishing polymorphisms in regulatory and protein-coding regions of genes differentially expressed in nonprogressors and progressors.
Description
62 pages. A thesis presented to the Department of Anthropology and the Clark Honors College of the University of Oregon in partial fulfillment of the requirements for degree of Bachelor of Science, Spring 2015.
Keywords
Molecular Anthropology, Simian Immunodeficiency Virus, SIV, Human Immunodeficiency Virus, Progressor, Nonprogressor, Bioinformatics, Immunology