KSHV latent infection alters the cellular microenvironment to increase glutamine utilization

The acidic microenvironment of tumor cells is mainly attributed to the increased production of lactic acid generated from glycolysis. Interestingly, cancer cells survive under these acidic microenvironments where normal cells would die. Additionally tumor cells utilize glutamine as a major carbon source.  Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi’s sarcoma, an endothelial based tumor. Similar to tumor cells, KSHV infected endothelial cells metabolize glucose generating elevated levels of lactic acid resulting in an acidic microenvironment, and glutamine is utilized as an alternative carbon source.  However the mechanism of how glutamine is metabolized in KSHV infected cells has not been elucidated. My project will focus on understanding how KSHV alters endothelial cells microenvironment to increase glutamine utilization. I propose that glutamine metabolism is enhanced by lactic acid production in KSHV infected endothelial cells. To test this, first, I will determine if the acid microenvironment increases glutamine utilization during KSHV latent infection. Second, I will evaluate if activity of enzymes involved in glutamine utilization is enhanced in the acidic microenvironment. My project will establish a relationship between acidic microenvironment and glutamine utilization in KSHV infected cells. It will provide a greater insight into metabolic changes that take place in KSHV infected endothelial cells and further the understanding of the metabolic needs and interactions of cells latently infected with an oncogenic herpesvirus.