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

Dittmer, D. P., Sanchez, E. L., Carroll, P. A., Thalhofer, A. B., & Lagunoff, M. (2015). Latent KSHV Infected Endothelial Cells Are Glutamine Addicted and Require Glutaminolysis for Survival. PLoS Pathogens, 11(7), e1005052.

Speaker: Ruei-Yi Chen (陳瑞怡)                    Time: 13:00~14:00

Commentator: Dr. Shun-hua Chen (陳舜華教授)       Place: Room 602

Abstract:

    Kaposi’s sarcoma-associated herpesvirus (KSHV; HHV-8) is an oncogenic, human γ-herpesvirus. The human diseases associated with KSHV are Kaposi’s sarcoma (KS), pleural effusion lymphoma and multicentric Castleman’s disease [1]. Many cancer cells use glutamine as a carbon source for maintenance of the tricarboxylic acid (TCA) cycle. Glutaminolysis is required to produce α-ketoglutarate (α-KG), which is the intermediate of the TCA cycle. Glutamine undergoes glutaminolysis to regulate the production of bioenergetics and biosynthetic precursors in TCA cycle [2]. This study showed that KSHV established a latent infection in the cultured human endothelial cells, which like cancer cells altered the catabolism of glutamine. KSHV infection increased exogenous glutamine uptake and the expression of glutamine transporter SLC1A5 through c-Myc / MondoAsignaling pathway. This study demonstrated that latent KSHV increased uptake of glutamine, and absence of glutamine leads to apoptosis of endothelial cells. Supplement of TCA cycle intermediates αKG increased KSHV survival. In conclusion, increased expression of glutamine transporter SLC1A5 during KSHV infection of endothelial cells, leads the cells to become glutamine addicted, and glutaminolysis is required for cell survival.

References:

1.    Berges, B.K. and A. Tanner, Modelling of human herpesvirus infections in humanized mice. J Gen Virol, 2014. 95(Pt 10): p. 2106-17.

2.    Yu, Y., A.J. Clippinger, and J.C. Alwine, Viral effects on metabolism: changes in glucose and glutamine utilization during human cytomegalovirus infection. Trends Microbiol, 2011. 19(7): p. 360-7.