Induction of the Warburg effect by Kaposi's sarcoma herpesvirus is required for the maintenance of latently infected endothelial cells
Induction of the Warburg effect by Kaposi's sarcoma herpesvirus is required for the maintenance of latently infected endothelial cells
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DOI：
10.1073/pnas.1004882107
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发表时间：
2010-06-08
影响因子：
11.1
通讯作者：
Lagunoff, Michael
中科院分区：
文献类型：
--
作者：
Delgado, Tracie;Carroll, Patrick A.;Lagunoff, Michael
卡波西肉瘤（KS）是非洲部分地区最常见的肿瘤，也是全世界艾滋病患者最常见的肿瘤。KS相关疱疹病毒（KSHV）是KS的病原体。虽然KS肿瘤包含许多细胞类型，但主要细胞是梭形细胞，一种维持KSHV潜伏期的内皮来源的细胞。KSHV激活许多细胞信号通路，但对KSHV如何在潜伏期改变细胞代谢知之甚少。瓦尔堡效应是大多数肿瘤细胞的常见代谢改变，其定义为有氧糖酵解的增加和氧化磷酸化作为能量来源的减少。瓦尔堡效应使细胞适应肿瘤环境，并且是肿瘤细胞存活所必需的。在内皮细胞的潜伏感染期间，KSHV诱导有氧糖酵解和乳酸产生，同时减少氧消耗，从而诱导瓦尔堡效应。糖酵解抑制剂选择性地诱导KSHV感染的内皮细胞凋亡，但不诱导未感染的内皮细胞凋亡。因此，与癌细胞类似，瓦尔堡效应对于维持KSHV潜伏感染的细胞是必需的。我们认为，KSHV诱导的瓦尔堡效应使受感染的细胞适应肿瘤微环境，有助于KS肿瘤的接种。此外，糖酵解抑制剂可能为潜伏性KSHV感染和最终KS肿瘤提供独特的治疗策略。
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.