The HIV-1 protein Nef is a critical factor in the viral pathogenesis and decline of CD4 T-cells during HIV infection. Nef has been implicated in modulating several cellular pathways, including apoptosis. This thesis herein describes our attempt to elucidate the mechanism by which Nef modulates apoptosis in T-cells. Using Jurkat cells inducibly expressing wild-type Nef, we observe that Nef renders cells more sensitive to apoptosis upon cross-linking with anti-Fas or TRAIL. Enhancement of Fas-mediated apoptosis required the presence of Lck, as apoptosis was abrogated in Nef expressing Lck-/- cells as compared to wild type Jurkat cells. Nef does not modulate expression of pro or anti-apoptotic proteins, or cell surface Fas receptor. Furthermore, Nef differentially mediates activation signaling pathways upon anti-CD3 stimulation. Enhancement of apoptosis by Nef may represent one of the mechanisms by which HIV depletes CD4 T-cells during infection.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.80295 |
| Date | January 2003 |
| Creators | Jao, Kevin |
| Contributors | Sekaly, Rafick-Pierre (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Microbiology and Immunology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 002032003, proquestno: AAIMQ98664, Theses scanned by UMI/ProQuest. |
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