Honors College
 

Document Type

Honors Thesis

Publication Date

Spring 5-2017

Abstract

The majority of the human population is infected with JC polyomavirus (JCPyV), which establishes an asymptomatic infection in the kidney of healthy individuals. In immunosuppressed individuals, the virus spreads to the brain and attacks glial cells, causing progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease. With limited treatments available, an improved understanding of the virus-host cell interactions during JCPyV infection is crucial for developing effective PML therapies. JCPyV internalization into host cells requires the serotonin 5- hydroxytryptamine type 2 (5-HT2) receptors. The mechanism by which the 5-HT2Rs mediate viral entry has not yet been characterized, yet it is thought to occur by clathrin- mediated endocytosis (CME). The objective of this research is to determine whether key 5-HT2R scaffolding proteins that mediate clathrin-dependent endocytosis are required for JCPyV infection. Reduction of cellular adaptor protein 2 (AP2), adaptor protein 180 (AP180), and clathrin by siRNA significantly reduced JCPyV infection, yet inhibition of calmodulin using a chemical calmodulin inhibitor had minimal effect on JCPyV infection. Taken together, these findings suggest these specific 5-HT2R scaffolding proteins are crucial for JCPyV infection. Additionally, this research is not limited to our understanding of JCPyV viral pathogenesis, a significant human pathogen with the potential to cause fatality, but can also be applied to understanding other neurotropic viruses or other viruses that enter by CME.

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