Degree Name
MS (Master of Science)
Program
Biology
Date of Award
5-2019
Committee Chair or Co-Chairs
Zhi Qiang Yao
Committee Members
Shunbin Ning, Ling Wang
Abstract
In this thesis, we investigated T cell homeostasis and DNA damage repair machineries in HIV infection. We found that the frequencies of CD4T cells were low, which is associated with cell apoptosis in HIV patients compared to healthy subjects. Importantly, these events were closely correlated to the increase in T cell exhaustion, senescence, DNA damage, and telomere attrition. Mechanistically, while the DNA damage sensors Mer11, Rad50, and NBS1 (MRN) complexes remained intact, the ataxia-telangiectasia mutated (ATM) kinase and its downstream checkpoint kinase 2 (CHK2) were significantly inhibited during HIV infection. Additionally, telomeric repeat-binding factor 2 (TRF2) that functions to protect telomeres from unwanted DNA damage was also suppressed by HIV infection. These findings revealed an important mechanism by which telomeres undergo DNA damage that remained unrepaired due to ATM deficiency and TRF2 deprotection - a process that could promote T cell apoptosis, senescence, and cellular dysfunction in HIV infection.
Document Type
Thesis - unrestricted
Recommended Citation
Nguyen, Lam, "Telomeric DNA Damage and Repair Machineries in HIV Infection" (2019). Electronic Theses and Dissertations. Paper 3536. https://dc.etsu.edu/etd/3536
Copyright
Copyright by the authors.