Degree Name

MS (Master of Science)

Program

Biology

Date of Award

12-2019

Committee Chair or Co-Chairs

Zhi Qiang Yao

Committee Members

Shunbin Ning, Ling Wang

Abstract

The clearance of viruses is largely dependent upon the activation of T cells to generate a robust immune response. However, host responses are suppressed during chronic viral infections. In this thesis, we explored the role of Top2α in DNA topology in individuals with chronic HBV, HCV, and HIV infections. We found that Top2α protein expression and activity were low in T cells derived from chronically virus-infected individuals compared to healthy subjects. Using CD4+ T cells treated with Top2α inhibitor or poisoner as a model, we demonstrated that Top2α inhibition disrupts the DNA topology, suppresses DNA repair kinase (ATM), and telomere protein (TRF2) expression, and induces T cell dysfunction. These findings reveal that Top2α inhibition is a mechanism by which viruses evade the host responses and establish persistent infection, and thus, restoring Top2α levels could be a way of boosting immune responses during chronic viral infections.

Document Type

Thesis - Withheld

Copyright

Copyright by the authors.

Available for download on Tuesday, October 31, 2023

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