Profiles
Bryan Mounce, Ph.D.
Assistant Professor
Education
PhD., Medical College of Wisconsin
Research Interests
Major Research Interests: Virus-host interactions at the metabolic interface.
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.
Publications
Mastrodomenico V, LoMascolo NJ, Cruz Pulido YE, Cunha CR, and Mounce BC. 2022. Polyamine-linked cholesterol incorporation in rift valley fever virus particles promotes infectivity. ACS Infectious Diseases. PMID: 35786847
LoMascolo NJ, Cruz Pulido YE, and Mounce BC. 2022. Bisacodyl limits chikungunya virus replication in vitro and is broadly antiviral. Antimicrobial Agents and Chemotherapy. PMID: 35652314
Hulsebosch BM and Mounce BC. 2021. Polyamine analog diethylnorspermidine restricts Coxsackievirus B3 infection and is overcome by 2A protease mutation in vitro. Viruses. PMID: 33669273
Firpo MR, Mastrodomenico VR, Hawkins GM, Prot M, Levillayer L, Gallagher T, Simon-Loriere E, and Mounce BC. 2020. Targeting polyamines by FDA-approved molecules inhibits coronavirus infection by reducing cellular attachment. ACS Infectious Diseases. PMID: 32966040
Mastrodomenico VR, Esin JJ, Qazi S, Khomutov M, Ivanov AV, Mukhopadhyay S, and Mounce BC. 2020. Virion-associated polyamines transmit with bunyaviruses to maintain infectivity and promote entry. ACS Infectious Diseases. PMID: 32687697
Firpo MR and Mounce BC. 2020. Diverse functions of polyamines in virus infection. Biomolecules 10(4):628. PMID: 32325677