Department of Cancer Biology, Abramson Family Cancer Research Institute, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Adv Virus Res. 2011;80:49-67. doi: 10.1016/B978-0-12-385987-7.00003-8.
Recent studies of human cytomegalovirus (HCMV) infection have demonstrated that the virus significantly alters cellular metabolism, especially the utilization of glucose and glutamine. Glucose is not broken down by the tricarboxylic acid (TCA) cycle in infected cells; instead, it is used biosynthetically for fatty acid synthesis for membranes needed during the infection. In this chapter, we discuss the possibility that HCMV integrates its mechanisms for manipulating cellular signaling and stress responses to induce novel adipocyte-like differentiation in order to alter metabolism so that glucose can be used synthetically, that is, for fatty acids and lipids. This process diverts glucose from the TCA cycle and requires induction of enzymes that can convert glutamine to α-ketoglutarate to maintain the TCA cycle (anaplerosis). We discuss data proposing that the anaplerotic utilization of glutamine may be mediated, in part, by c-Myc activation, and the induction of adipocyte-like differentiation may result from the activation of the endoplasmic reticulum resident kinase PKR-like ER kinase. These alterations in metabolism during HCMV infection are comparable to those seen in many tumor cells. Indeed, the alterations in cellular signaling, stress responses, and metabolism that have been characterized could result in unexpected pathogenesis, potentially implicating HCMV as an agent or subtle cofactor in many maladies. Better understanding of HCMV's effects on cell signaling and metabolism will show how HCMV-mediated modifications of cellular processes relate to pathogenesis and will suggest novel avenues for antiviral therapy.
最近对人类巨细胞病毒 (HCMV) 感染的研究表明，该病毒会显著改变细胞代谢，尤其是对葡萄糖和谷氨酰胺的利用。在感染细胞中，葡萄糖不会通过三羧酸 (TCA) 循环分解；相反，它被用于生物合成脂肪酸，以合成感染期间所需的膜。在本章中，我们讨论了 HCMV 整合其操纵细胞信号和应激反应的机制以诱导新的脂肪细胞样分化的可能性，从而改变代谢，以便可以将葡萄糖用于合成，即用于脂肪酸和脂质。这个过程将葡萄糖从 TCA 循环中转移出来，并需要诱导可以将谷氨酰胺转化为α-酮戊二酸以维持 TCA 循环（氨补充）的酶。我们讨论了部分数据，这些数据表明谷氨酰胺的氨补充利用可能部分由 c-Myc 激活介导，而脂肪细胞样分化的诱导可能来自内质网驻留激酶 PKR 样 ER 激酶的激活。在 HCMV 感染期间，这些代谢的改变与许多肿瘤细胞中看到的改变相似。事实上，已经确定的细胞信号、应激反应和代谢的改变可能导致意想不到的发病机制，这可能使 HCMV 成为许多疾病的潜在病原体或微妙的协同因子。更好地了解 HCMV 对细胞信号和代谢的影响将显示 HCMV 介导的细胞过程修饰与发病机制的关系，并为抗病毒治疗提供新的途径。
