Aiden Pike

Document Type

Honors Thesis

Major

Biochemistry & Molecular and Cellular Biology

Advisor(s)

Melissa Maginnis

Committee Members

Ana Chatenever, Benjamin King, Sally Molloy

Graduation Year

2023

Publication Date

2025

Abstract

JC polyomavirus (JCPyV) is a ubiquitous human virus which causes a persistent, asymptomatic kidney infection in up to 80% of the healthy adult population. In immunocompromised patients, such as those with HIV/AIDS or those taking prescribed immunomodulatory drugs, JCPyV traffics to the central nervous system and can induce progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease. The mechanisms of JCPyV infection remain poorly understood, and there is no approved treatment for PML. However, studying virus-host cell interactions can reveal novel targets for treatment. Previous evidence from the Maginnis laboratory has implicated intracellular calcium and immune signaling in JCPyV infection after viral entry into the host cell. The goal of this project was to determine the role of inflammatory and calmodulin-dependent protein kinase IV (CaMKIV) signaling in regulating JCPyV infection. Gene expression profiles of primary and immortalized cell lines during infection indicated a reduced expression in immune-responsive genes in immortalized cells, particularly NF-κB, a downstream target of CaMKIV signaling. Analysis of non-coding control regions from JCPyV isolates revealed differential detection of NF-κB binding sites in viral genomes of healthy vs. PML patients. Neither chemical inhibition of CaMKIV activity nor siRNA knockdown resulted in a significant reduction in JCPyV infection, indicating that CaMKIV likely does not play a role in JCPyV infection. Finally, treatment with increasing concentrations of glucose simultaneously reduced infection and increased viral protein production. The research reported in this thesis does not support a role for CaMKIV in JCPyV infection, yet reveals interesting characteristics in gene profiles and stark implications of transcription factor binding site frequencies as a result of viral genome rearrangements during infection.

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