Use of viruses to study cancer metabolism



Viruses hijack host cell metabolism to promote increased nutrient uptake and anabolism 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 (Thai et al, Cell Metabolism, 2014). How adenovirus-induced MYC activation leads to selective transcription of target genes remains unknown. Additionally, the specific compilation of metabolic genes altered by adenovirus infection is currently undefined. In addition to increasing glucose metabolism, we found adenovirus infection also enhances anabolic glutamine metabolism by an unknown mechanism.  We are now defining the mechanistic events necessary for these virus-induced metabolic changes and the impact they have on anabolic metabolism and virus replication, with the goal of identifying key enzymes essential for anabolism in cancer cells.  Because viruses are so efficient at reprogramming host cell metabolism towards increased anabolism, they represent a powerful tool to identify important metabolic enzymes for anabolic metabolism, and potentially the most promising cancer metabolism drug targets. 



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