Latent KSHV Infected Endothelial Cells Are Glutamine Addicted and Require Glutaminolysis for Survival

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KSHV is the etiologic agent of KS, the most common tumor of AIDS patients worldwide. Currently, there are no therapeutics available to directly treat latent KSHV infection. This study reveals that latent KSHV infection induces endothelial cells to become glutamine addicted, similarly to cancer cells. Extracellular glutamine is required to feed the TCA cycle through glutaminolysis, a process called anaplerosis. KSHV induces protein expression of the glutamine transporter SLC1A5 and SLC1A5 expression is required for the survival of latently infected cells. KSHV also induces the expression of the proto-oncogene Myc and its binding partner Max, as well as, the nutrient-sensing transcription factor, MondoA and its binding partner Mlx. MondoA regulates SLC1A5 and glutaminolysis during latent KSHV infection, and its expression is required for the survival of latently infected endothelial cells. These studies show that glutaminolysis and a single glutamine transporter, under the regulation of MondoA, are required for the survival of latently infected cells, providing novel druggable targets for latently infected endothelial cells. This work supports that a cancer-like metabolic signature is established by latent KSHV infection, opening the door to further therapeutic targeting specifically of KSHV latently infected cells.

Vyšlo v časopise: Latent KSHV Infected Endothelial Cells Are Glutamine Addicted and Require Glutaminolysis for Survival. PLoS Pathog 11(7): e32767. doi:10.1371/journal.ppat.1005052
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005052

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