Date of Award

2021

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Microbiology and Immunology

Abstract

Non-polioenteroviruses are highly infectious viruses that typically cause mild asymptomatic cases but can cause severe disease such as aseptic meningitis and dilated cardiomyopathy. Coxsackievirus B3 (CVB3) is a member of this group and is prevalent in the United States and Eastern Asia. Viruses like CVB3 rely on the host cell for many molecules in order to replicate. One such set of molecules is the polyamines. Polyamines are small, positively charged molecules that play a role in a multitude of cellular processes including RNA/DNA stabilization, gene expression, translation, and regulating membrane fluidity. Previous studies have shown CVB3 relies on polyamines for cellular attachment: when polyamines are depleted from the cell CVB3 attachment is attenuated. We hypothesized that this may be due to changes in expression of heparan sulfate proteoglycans. Heparan sulfate proteoglycans (HSPGs) are ubiquitously expressed on eukaryotic cells and make up the majority of the glycocalyx layer. HSPGs have been implicated in viral attachment mechanisms; thus, we investigated whether polyamines interacted with HSPGs to facilitate CVB3 attachment to cells. We found that CVB3 uses both polyamines and HSPGs to attach to cells and when either polyamines or HSPGs are depleted CVB3 can mutate its genome to escape these blockages to attach and infect cells. This work highlights a basic role of polyamines in HSPG synthesis and function and demonstrates the connection between these two pathways that CVB3 uses to replicate.

Creative Commons License

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

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