Induction of the Warburg effect by Kaposi's sarcoma herpesvirus is required for the maintenance of latently infected endothelial cells

被引:197
作者
Delgado, Tracie [1 ]
Carroll, Patrick A. [1 ]
Punjabi, Almira S. [1 ]
Margineantu, Daciana [2 ]
Hockenbery, David M. [2 ]
Lagunoff, Michael [1 ]
机构
[1] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA
[2] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA
关键词
human herpesvirus-8; gamma-herpesvirus; latency; glycolysis; DE-NOVO INFECTION; CANCER-CELLS; HYPOXIA; GLYCOLYSIS; MITOCHONDRIA; METABOLISM; ACTIVATION; HEXOKINASE-2; ADAPTATION; EXPRESSION;
D O I
10.1073/pnas.1004882107
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
Kaposi's sarcoma (KS) is the most commonly reported tumor in parts of Africa and is the most common tumor of AIDS patients worldwide. KS-associated herpesvirus (KSHV) is the etiologic agent of KS. Although KS tumors contain many cell types, the predominant cell is the spindle cell, a cell of endothelial origin that maintains KSHV latency. KSHV activates many cell-signaling pathways but little is known about how KSHV alters cellular metabolism during latency. The Warburg effect, a common metabolic alteration of most tumor cells, is defined by an increase in aerobic glycolysis and a decrease in oxidative phosphorylation as an energy source. The Warburg effect adapts cells to tumor environments and is necessary for the survival of tumor cells. During latent infection of endothelial cells, KSHV induces aerobic glycolysis and lactic acid production while decreasing oxygen consumption, thereby inducing the Warburg effect. Inhibitors of glycolysis selectively induce apoptosis in KSHV-infected endothelial cells but not their uninfected counterparts. Therefore, similar to cancer cells, the Warburg effect is necessary for maintaining KSHV latently infected cells. We propose that KSHV induction of the Warburg effect adapts infected cells to tumor microenvironments, aiding the seeding of KS tumors. Additionally, inhibitors of glycolysis may provide a unique treatment strategy for latent KSHV infection and ultimately KS tumors.
引用
收藏
页码:10696 / 10701
页数:6
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