Date of Award
2026
Degree Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Microbiology and Immunology
First Advisor
Bryan Mounce
Abstract
Polyamines are essential for regulating translation, cell cycling, and nucleic acid metabolism, but their broader metabolic roles are unclear. We previously showed that polyamines influence cholesterol metabolism, and here, we extend this to global lipid metabolism. Polyamine depletion increases the number and size of lipid droplets, likely due to reduced fatty acid oxidation, mitochondrial respiration, and altered mitochondrial morphology. Inhibitors of polyamine and lipid metabolism are broadly antiviral, suggesting these pathways as potential antiviral targets. Using metabolomics, we investigated these lipid alterations during Coxsackievirus B3 infection, a lipid-dependent virus. Using a drug screen, we found that lysophosphatidic acid (LPA) signaling via LPA receptor 1 (LPAR1) is critical for viral replication. Blocking LPAR1 reduced viral replication and cellular lipid droplet abundance by inhibiting the fatty acid synthesis pathway. These results identify the LPA-LPAR1 axis as a key metabolic regulator of RNA virus infection.
Recommended Citation
LoMascolo, Natalie J., "Defining the Metabolic Requirements of RNA Virus Replication: Polyamines, Mitochondrial Energetics, and Lipids" (2026). Dissertations. 4312.
https://ecommons.luc.edu/luc_diss/4312
