ArticleViruses2019
Coxsackievirus B3 Responds to Polyamine Depletion via Enhancement of 2A and 3C Protease Activity.
Article in Viruses, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Polyamines as Gatekeepers of Virus Replication and Central Nervous System Homeostasis.Pathogens (Basel, Switzerland) · 2026Review
- Identification of picornavirus proteins that inhibit de novo nucleotide synthesis during infection.PLoS pathogens · 2025Article
- Defence Warriors: Exploring the crosstalk between polyamines and oxidative stress during microbial pathogenesis.Redox biology · 2025Review
- Update on enteroviral protease 2A: Structure, function, and host factor interaction.Biosafety and health · 2023Review
- Good cop, bad cop: Polyamines play both sides in host immunity and viral replication.Seminars in cell & developmental biology · 2023Review
- Article
- Polyamines and eIF5A hypusination facilitate SREBP2 synthesis and cholesterol production leading to enhanced enterovirus attachment and infection.PLoS pathogens · 2023Article
- Polyamine-Linked Cholesterol Incorporation in Rift Valley Fever Virus Particles Promotes Infectivity.ACS infectious diseases · 2022Article
- PEDV infection affects the expression of polyamine-related genes inhibiting viral proliferation.Virus research · 2022Article
- Potential Antiviral Action of Alkaloids.Molecules (Basel, Switzerland) · 2022Review
- Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2.Science (New York, N.Y.) · 2021Article
- Polyamine Analog Diethylnorspermidine Restricts Coxsackievirus B3 and Is Overcome by 2A Protease Mutation In Vitro.Viruses · 2021Article
- Polyamine regulation of porcine reproductive and respiratory syndrome virus infection depends on spermidine-spermine acetyltransferase 1.Veterinary microbiology · 2020Article
- Diverse Functions of Polyamines in Virus Infection.Biomolecules · 2020Review
- Targeting Polyamine Metabolism for Control of Human Viral Diseases.Infection and drug resistance · 2020Review
- Polyamine Depletion Abrogates Enterovirus Cellular Attachment.Journal of virology · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Polyamines are small positively-charged molecules abundant in eukaryotic cells that are crucial to RNA virus replication. In eukaryotic cells, polyamines facilitate processes such as transcription, translation, and DNA replication, and viruses similarly rely on polyamines to facilitate transcription and translation. Whether polyamines function at additional stages in viral replication remains poorly understood. Picornaviruses, including Coxsackievirus B3 (CVB3), are sensitive to polyamine depletion both in vitro and in vivo; however, precisely how polyamine function in picornavirus infection has not been described. Here, we describe CVB3 mutants that arise with passage in polyamine-depleted conditions. We observe mutations in the 2A and 3C proteases, and we find that these mutant proteases confer resistance to polyamine depletion. Using a split luciferase reporter system to measure protease activity, we determined that polyamines facilitate viral protease activity. We further observe that the 2A and 3C protease mutations enhance reporter protease activity in polyamine-depleted conditions. Finally, we find that these mutations promote cleavage of cellular eIF4G during infection of polyamine-depleted cells. In sum, our results suggest that polyamines are crucial to protease function during picornavirus infection. Further, these data highlight viral proteases as potential antiviral targets and highlight how CVB3 may overcome polyamine-depleting antiviral therapies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.