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The Levinson Emerging Scholars ProgramAlexandra Taipale - Biochemistry
Mentor: James Mullins, Microbiology Project Title: Sex Differences in Viral Evolutionary Trends Associated with the Progression of Human Immunodeficiency Virus Type 1 Infection Abstract: The effect of viral evolution on the duration of latent Human Immunodeficiency Virus Type 1 (HIV-1) infection has been studied extensively in men. The asymptomatic latency period, after HIV-1 infection and before the onset of Acquired Immune Deficiency Syndrome (AIDS), is characterized by high viral variability. In many cases, a viral phenotype that utilizes CXCR4 and/or CCR5 receptors on target host cells to advance HIV-1 progression also emerges during this period. Despite known sex-dependent variation in the progression of HIV-1, the effect of viral evolution and CXCR4/CCR5 utilizing virus (X4 virus) prevalence on HIV-1 latency has not yet been studied in women. I will investigate trends in viral evolution in 9 women from seroconversion to the development of AIDS. I will then compare my results to previously studied male viral evolutionary trends. Over the course of three quarters, a total of 72 blood plasma samples, an average of 8 samples from each woman collected progressively during the course of infection, will be used to generate 25-30 HIV-1 sequences per time point. These sequences will then be evaluated through 1) viral divergence from a founder strain 2) viral population diversity and 3) emergence and prevalence of X4 viruses. I will then analyze the effect of viral evolutionary trends and X4 virus prevalence on the duration of HIV-1 infection before the onset of AIDS. Ultimately, a comparison between the sexes will be made. Furthering the scientific communities’ knowledge of sex-related HIV-1 infection variation could lead to more effective sex-specific treatment and vaccine development. The important biological question of whether sex can influence HIV-1’s evolutionary path will be addressed. |
