Viral activation of cellular metabolism

Abstract

To ensure optimal environments for their replication and spread, viruses have evolved to alter many host cell pathways. In the last decade, metabolomic studies have shown that eukaryotic viruses induce large-scale alterations in host cellular metabolism. Most viruses examined to date induce aerobic glycolysis also known as the Warburg effect. Many viruses tested also induce fatty acid synthesis as well as glutaminolysis. These modifications of carbon source utilization by infected cells can increase available energy for virus replication and virion production, provide specific cellular substrates for virus particles and create viral replication niches while increasing infected cell survival. Each virus species also likely requires unique metabolic changes for successful spread and recent research has identified additional virus-specific metabolic changes induced by many virus species. A better understanding of the metabolic alterations required for the replication of each virus may lead to novel therapeutic approaches through targeted inhibition of specific cellular metabolic pathways.

Keywords: Fatty acid synthesis; Glutaminolysis; Glycolysis; Metabolism; Metabolomics; Virus.

Figure 1. Virus infection alters host cell metabolism

Major metabolic pathways altered by virus infection are highlighted, glycolysis (Green), Fatty Acid Synthesis, FAS (Orange), Glutaminolysis (Purple), Pentose Phosphate Pathway, PPP (Dark Blue). Glucose enters the cell and is metabolized to glucose-6-phosphate (G-6-P) which can be shunted to the Pentose Phosphate Pathway (PPP) to support nucleotide synthesis, or to pyruvate. Pyruvate can be converted to lactate via glycolysis, which is secreted from the cell, or Acetyl-CoA (ACoA), which enters the TCA cycle. Citrate can be shunted out of the mitochondria to enter FAS. Glutamine enters the cell and is deaminated twice to form aKG and ammonia (NH₃). αKG can then enter the TCA cycle. Major enzymes of carbon metabolism are in turquoise and discussed in main text.