Viruses Behaving Badly: How Viruses Subvert Cellular Metabolism to Replicate

As obligate intracellular pathogens, viruses require host-derived nucleotides, amino acids, and lipids, among others, and the bioavailability of these metabolites can restrict or promote virus infection. Additionally, viruses alter cellular metabolism to foster replication, by promoting cell cycle, enhancing synthetic enzyme activity, or inhibiting catabolic enzymes. Additionally, large DNA viruses encode entire biosynthetic pathways. In contrast, RNA viruses have limited genomic capacity to encode metabolic enzymes and rely on host metabolism to support replication. Additionally, several antiviral molecules directly or indirectly affect metabolism, including classic molecules like ribavirin, which inhibits IMPDH and de novo guanine synthesis to quell virus replication. Further, cellular metabolic state varies between cell type and even individual cells within a population. We study how RNA viruses interact with cellular metabolism, with particular focus on molecules called polyamines. These polyamines are crucial for virus replication, and we can target their synthesis with small molecule inhibitors. We study how viruses use polyamines, how viruses manipulate polyamines, and how the cell fights back to prevent viruses from obtaining polyamines. Through this work, we discover new ways that viruses infect, identify potential drug targets, and investigate a unique way that RNA viruses interface with cellular metabolism.