Date of Award

2019

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Microbiology and Immunology

Abstract

Polyamines are small polycationic molecules with flexible carbon chains that are found in all eukaryotic cells. Polyamines are involved in the regulation of many host processes and have been shown to be implicated in viral replication. Depletion of polyamine pools in cells with FDA approved drugs restricts replication of diverse RNA viruses. Viruses can exploit host polyamines to facilitate packaging, transcription, translation, and protease activity but other mechanisms remain largely unknown. Picornaviruses, including Coxsackievirus B3 (CVB3), are sensitive to depletion of polyamines and remain a significant public health threat. We employed CVB3 as a model system to investigate a potential pro-viral role for polyamines using a forward screen. Passaging CVB3 in polyamine depleted cells generated a mutation in capsid protein VP3 at residue 234, which is involved in receptor binding. We show this mutation confers resistance to polyamine depletion. Through attachment assays, we demonstrate that polyamines facilitate CVB3 attachment to susceptible cells, and that the capsid mutant rescues this inhibition in polyamine depleted cells. More divergent viruses also exhibited reduced attachment to polyamine depleted cells, suggesting that polyamines may facilitate attachment of diverse RNA viruses. Virus-receptor interactions are involved in the pathogenesis, transmission, and host range of viruses; thus understanding this process is crucial to combating virus infection. Further, these studies inform additional mechanisms of action for polyamine-depleting pharmaceuticals with implications for potential antiviral therapies.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

Available for download on Friday, August 13, 2021

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