Date of Award
12-11-2023
Degree Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Microbiology and Immunology
First Advisor
Bryan Mounce
Abstract
Polyamines are small positively charged alkylamines found in all living cells. These ubiquitous molecules have been found to play a variety of roles ranging from stabilizing nucleic acids (DNA and RNA) to cellular proliferation. Studies have also identified roles for polyamines in viral packaging and viral enzyme function. However, the role of polyamines on cellular components and their effect on viral replication is less known. In our efforts to identify the lipid-polyamine metabolic connection to virus replication we utilized a human hepatocyte cell line in which polyamines were depleted via pharmacological or genetic approaches and studied the effects on lipid metabolism and viral replication by using chikungunya virus (CHIKV) as a model virus. We identified a role for polyamines in lipid metabolism. More specifically, we observed that polyamine depletion resulted in the accumulation and enlargement of lipid droplets in hepatocytes. This accumulation of lipid droplets was observed to be the result of reduced fatty acid oxidation rather than enhanced de novo lipogenesis. Furthermore, we observed that inhibition of fatty acid oxidation or lipogenesis reduced viral titers of CHIKV. However, exogenous addition of a fatty acid such as oleic acid rescued viral titers in polyamine depleted cells.
Recommended Citation
Cruz Pulido, Yazmin Edith, "Establishing a Novel Lipid-Polyamine Metabolic Connection to Virus Replication" (2023). Dissertations. 4071.
https://ecommons.luc.edu/luc_diss/4071
