Date of Award
2021
Degree Type
Thesis
Degree Name
Master of Science (MS)
Department
Microbiology and Immunology
Abstract
Enteroviruses, including Coxsackievirus B3 (CVB3), are pervasive pathogens that cause significant disease, including cardiomyopathies. Unfortunately, no treatments or vaccines are available for infected individuals. We identified the host polyamine pathway as a potential drug target, as inhibiting polyamine biosynthesis significantly reduces enterovirus replication in vitro and in vivo. Here, we show that CVB3 is sensitive to polyamine depletion through the polyamine analog diethylnorspermidine (DENSpm) which enhances polyamine catabolism through induction of polyamine acetylation. We demonstrate that CVB3 acquires resistance to DENSpm via mutation of the 2A protease, which enhances proteolytic activity in the presence of DENSpm. Resistance to DENSpm occurred via mutation of a non-catalytic site mutation and results in decreased fitness. These data demonstrate the potential for targeting polyamine catabolism as an antiviral therapy as well as highlight a potential mechanism of resistance.
Recommended Citation
Hulsebosch, Bridget, "Characterizing a Novel Cocksackievirus B3 Protease Mutant and Its Response to Polyamine Depletion" (2021). Master's Theses. 4361.
https://ecommons.luc.edu/luc_theses/4361
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.
Copyright Statement
Copyright © 2021 Bridget Hulsebosch
