"Changes in glucose and glutamine utilization during KSHV infection"
Kaposi's Sarcoma-Associated Herpesvirus (KSHV) is the etiologic agent of Kaposi's Sarcoma, an endothelial-based tumor. Similarly to tumor cells, KSHV infected endothelial cells metabolize glucose preferentially through fermentation rather than oxidative phosphorylation, a process known as the Warburg effect. To support altered metabolism, tumor cells derive additional energy by hyperactiviating the conversion of glutamine to glutamate onto alpha-ketoglutarate, to enter into the TCA cycle and promote macromolecular biosynthesis. While it is known how glutamine is metabolized in tumor cells, glutamine metabolism in KSHV infected cells has not yet been explored.
The Lagunoff lab has established that glucose is required during KSHV infection. In addition to glucose, I hypothesize that KSHV modulates glutamine utilization to sustain viral oncogenic infection. My project will focus on understanding how KSHV infected endothelial cells modulate both glucose and glutamine utilization and the cell signaling mechanisms involved to maintain cell survival. I will perform a metabolic flux analysis to track the fate of carbon through the glucose and glutamine utilization pathways, and I will quantify alterations of kinase activity using a phosphoproteomics approach. My project will establish that glutamine is required to generate intermediates for the TCA cycle and thus improve understanding of the mechanism of glucose and glutamine utilization during KSHV pathogenesis. Ultimately, these studies will provide a greater insight into metabolic and cell signaling changes that take place in KSHV infected endothelial cells and further the understanding of metabolic needs and interactions of cells latently infected with an oncogenic herpesvirus.