Author's School

Graduate School of Arts & Sciences

Author's Department/Program

Biology and Biomedical Sciences: Molecular Microbiology and Microbial Pathogenesis

Language

English (en)

Date of Award

Summer 9-1-2014

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Chair and Committee

David Wang

Abstract

The family Polyomaviridae is comprised of small, double-stranded DNA viruses of approximately 5,000 base pairs. Two polyomaviruses are well-established human pathogens and cause significant morbidity and mortality in immunocompromised patients. These viruses were discovered in the 1970s, but the last seven years have seen an explosion of novel human polyomavirus discoveries. The work described here seeks to address two questions: "Are there additional, novel polyomaviruses infecting humans?" and "Do these polyomaviruses cause disease in their human hosts?" The discovery of an additional novel polyomavirus, MW polyomavirus (MWPyV), is described. MWPyV was discovered in the stool of a healthy child from Malawi but was subsequently detected from pediatric patients with diarrhea in St. Louis, Missouri. As a step toward determining the pathogenicity of WU polyomavirus (WUPyV) and KI polyomavirus (KIPyV) in humans, immunohistochemical studies were completed to identify their tissue and cell tropisms. Both viruses were detected in alveolar macrophages, and WUPyV was also detected in respiratory epithelial cells and in cells associated with mucin-producing cells in the trachea. In addition, KIPyV was detected in the spleen. The immunocompromised state of the patients studied raises important questions about the role of immunosuppression in the pathogenesis of WUPyV and KIPyV. Finally, this work details ultimately unsuccessful attempts to establish a cell culture system for WUPyV, which would have provided a means to study viral biology and disease causality. Overall, these studies further our understanding of human polyomavirus biology and the role of WUPyV and KIPyV in human disease and provide additional avenues for future research to further address these important questions.

Comments

This work is not available online per the author’s request. For access information, please contact digital@wumail.wustl.edu or visit http://digital.wustl.edu/publish/etd-search.html.

Permanent URL: http://dx.doi.org/10.7936/K7ZG6Q89

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