Department of Cancer Biology, Abramson Family Cancer Research Institute, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Trends Microbiol. 2011 Jul;19(7):360-7. doi: 10.1016/j.tim.2011.04.002. Epub 2011 May 12.
Human cytomegalovirus (HCMV) infection causes dramatic alterations of intermediary metabolism, similar to those found in tumor cells. In infected cells, glucose carbon is not completely broken down by the tricarboxylic acid (TCA) cycle for energy; instead, it is used biosynthetically. This process requires increased glucose uptake, increased glycolysis and the diversion of glucose carbon, in the form of citrate, from the TCA cycle for use in HCMV-induced fatty acid biosynthesis. The diversion of citrate from the TCA cycle (cataplerosis) requires induction of enzymes to promote glutaminolysis, the conversion of glutamine to α-ketoglutarate to maintain the TCA cycle (anaplerosis) and ATP production. Such changes could result in heretofore uncharacterized pathogenesis, potentially implicating HCMV as a subtle cofactor in many maladies, including oncogenesis. Recognition of the effects of HCMV, and other viruses, on host cell metabolism will provide new understanding of viral pathogenesis and novel avenues for antiviral therapy.
人类巨细胞病毒（HCMV）感染会导致中间代谢发生剧烈变化，类似于肿瘤细胞中发现的变化。在受感染的细胞中，葡萄糖碳不完全通过三羧酸（TCA）循环分解产生能量，而是用于生物合成。这个过程需要增加葡萄糖摄取，增加糖酵解，并将 TCA 循环中的柠檬酸形式的葡萄糖碳转移，用于 HCMV 诱导的脂肪酸生物合成。柠檬酸从 TCA 循环中的转移（脱羧作用）需要诱导酶来促进谷氨酰胺分解，将谷氨酰胺转化为α-酮戊二酸，以维持 TCA 循环（补充作用）和 ATP 产生。这些变化可能导致迄今为止尚未描述的发病机制，可能使 HCMV 成为许多疾病（包括肿瘤发生）的微妙协同因子。认识到 HCMV 和其他病毒对宿主细胞代谢的影响将为病毒发病机制提供新的认识，并为抗病毒治疗开辟新途径。
