Polyamine Analog Diethylnorspermidine Restricts Coxsackievirus B3 and Is Overcome by 2A Protease Mutation In Vitro
1
Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA
2
Infectious Disease and Immunology Research Institute, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Petri Susi
Viruses 2021, 13(2), 310; https://doi.org/10.3390/v13020310
Received: 12 January 2021
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Revised: 10 February 2021
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Accepted: 12 February 2021
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Published: 16 February 2021
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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 that potential for targeting polyamine catabolism as an antiviral target as well as highlight a potential mechanism of resistance.
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Keywords:
Coxsackievirus; polyamines; enterovirus; protease
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MDPI and ACS Style
Hulsebosch, B.M.; Mounce, B.C. Polyamine Analog Diethylnorspermidine Restricts Coxsackievirus B3 and Is Overcome by 2A Protease Mutation In Vitro. Viruses 2021, 13, 310. https://doi.org/10.3390/v13020310
AMA Style
Hulsebosch BM, Mounce BC. Polyamine Analog Diethylnorspermidine Restricts Coxsackievirus B3 and Is Overcome by 2A Protease Mutation In Vitro. Viruses. 2021; 13(2):310. https://doi.org/10.3390/v13020310
Chicago/Turabian StyleHulsebosch, Bridget M., and Bryan C. Mounce. 2021. "Polyamine Analog Diethylnorspermidine Restricts Coxsackievirus B3 and Is Overcome by 2A Protease Mutation In Vitro" Viruses 13, no. 2: 310. https://doi.org/10.3390/v13020310
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