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 - unrestricted
Recommended Citation
Ogbu, Stella Chinyere, "Role of Topoisomerase II alpha in DNA Topology and T cell responses during Chronic Viral Infections" (2019). Electronic Theses and Dissertations. Paper 3661. https://dc.etsu.edu/etd/3661
Copyright
Copyright by the authors.