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They're small, they're positively-charged and they're important - both for the cell and viruses. We're trying to figure out why they're important and how we can target polyamines to combat viral infection.
Viruses and cells battle for resources: the virus usurps cellular resources to replicate itself and produce more viruses, while the cell uses its resources to fight back against viral infection and maintain its own processes. The Mounce lab focuses on how viruses and cells compete for polyamines, a valuable resource for both.
Polyamines are small, positively charged molecules that have several functions in the context of the cell, including roles in nucleic acid conformation, regulating the cell cycle, and altering cellular translation. In addition, polyamines are important for many different viruses, from chikungunya virus to enterovirus to rabies virus. We are interested in how viruses use polyamines, as well as how viruses and cells “fight” for polyamines. Further, the polyamine pathway is a notable therapeutic target, so we are also interested in how we can use inhibitors of polyamine biosynthetic enzymes to treat viral infection and, perhaps, other diseases.
Polyamines in cellular processes
During viral infection, the interferon response is triggered to limit viral replication. One way the cell limits viral replication is by depleting polyamines, through the enzyme SAT1. SAT1 acetylates polyamines, reversing their charges and clearing them from the cell. The effect this has on the cell isn’t known, however. Thus, we are interested in determining how polyamines may impact cellular signaling and what impact this has on viral replication.
Polyamines in viral processes
Our previous work has demonstrated that chikungunya and Zika viruses rely on polyamines for translation of the viral genomes and to stimulate the RNA polymerase. However, precisely how polyamines are involved in these processes isn’t entirely understood. We are working to understand how polyamines affect these processes, as well as others, in diverse viruses like Zika virus, Coxsackievirus, enterovirus, and vesicular stomatitis virus. Understanding how viruses rely on polyamines can inform how we can better treat viral infection with inhibitors, develop new inhibitors, or use combination therapies. We are also interested in how viruses evolve to overcome polyamine depletion, which has important implications for antiviral resistance.
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