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.
| Identifer | oai:union.ndltd.org:ETSU/oai:dc.etsu.edu:etd-5001 |
| Date | 01 May 2019 |
| Creators | Nguyen, Lam |
| Publisher | Digital Commons @ East Tennessee State University |
| Source Sets | East Tennessee State University |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Electronic Theses and Dissertations |
| Rights | Copyright by the authors. |
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