Use of Viruses to Study Cancer Metabolism

Viruses are powerful tools to study cancer metabolism. They trigger major metabolic changes in host cells to meet the bioenergetic and biosynthetic demands of virus infection - changes similar to the enhanced glycolysis and anabolic metabolism widely observed in cancer cells. However, unlike cancer cells, viruses undergo intense selection for efficiency, and rapidly and robustly reprogram host cell metabolism through activation of specific key flux-altering nodes, rather than whole metabolic pathway gene sets. We recently reported that adenovirus infection increases host cell anabolic glucose metabolism via MYC activation of specific metabolic target genes, only a subset of those turned on by MYC in many cancers. We are now investigating how adenovirus-induced MYC activation leads to selective transcription of target genes. Additionally, we have generated a list of the specific metabolic genes altered by adenovirus infection and are examining their role in anabolic metabolism, virus replication, and cancer proliferation. Because viruses are so efficient at reprogramming host cell metabolism towards increased anabolism, they represent a powerful tool to identify the most important metabolic enzymes for anabolic metabolism, and potentially the most promising cancer metabolism drug targets.