Figure 12. Schematic diagram showing the pathways for glutamate generation and mGluR1 upregulation in KSHV infected cells.

During latent infection, KSHV LANA-1 protein activates c-Myc, which leads to the upregulation of glutaminase and induction of glutamate release. Dashed line denotes c-Myc regulation and glutaminase expression. KSHV latent viral protein Kaposin A binds and sequesters REST in the cell cytoplasm, which in turn relieves the REST mediated suppression of the mGluR1 gene and upregulates expression of the mGluR1 receptor. Binding of glutamate to mGluR1 induces signaling and proliferation of infected cells. These studies show that proliferation of cancer cells latently infected with KSHV in part depends upon glutamate and glutamate receptor and therefore could potentially be used as therapeutic targets for the control and elimination of KSHV associated cancers.