HCMV infection dramatically alters cellular metabolism, this review focuses on how the virus alters glucose and glutamine metabolism and fatty acid synthesis. Changes to glucose metabolism include increased glucose uptake through the induction of the glucose transporter GLUT4, upregulation of glycolytic enzymes and probable allosteric activation of glycolysis. Although these changes are rather dramatic they are likely to represent only a fraction of the metabolic changes wrought by HCMV infection. Such changes are likely to contribute to forms of HCMV pathogenesis that could be very different from those that have been studied and documented to this point. For example, HCMV and other viruses which induce metabolic changes similar to HCMV might play a greater role in oncogenesis than previously recognized. At this point, our understanding of the mechanisms used by HCMV to alter metabolic processes is very limited and requires further study.
Viral effects on metabolism: changes in glucose and glutamine utilization during human cytomegalovirus infection. Trends Microbiol. May 11 2011
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.