Feline Immunodeficiency Virus (FIV) and Human Immunodeficiency Virus (HIV) are lentiviruses that are remarkable similar in their genomic organization, receptor usage and pathogenesis. Based on this FIV has evolved into a well-established small animal model for studying AIDS. FIV and HIV cause a progressive depletion of T cells via a still unknown mechanism though numerous studies support a role of membrane expressed HIV env glycoprotein in apoptotic killing of CD4+ T cells. HIV env glycoprotein is a heterodimer of surface expressed gp120 that binds to CD4 and a chemokine receptor and transmembrane gp41 that mediates fusion and syncytia formation. The role of the fusion process in HIV env-mediated apoptosis remains controversial even though evidence suggests that cytopathic effect of HIV is related to the fusogenic potential of env glycoprotein. Blocking HIV env receptor interactions either at the level of gp120 or gp41 blocks both syncytia formation and apoptosis. This suggests a crucial role for HIV gp41 in fusion, as well as apoptosis. The hydrophobic pre-transmembrane (pre-TM) region of HIV gp41 is important for membrane fusion and sequence analysis reveals a similar region in FIV gp41. The current study was undertaken to determine the role of different regions of FIV env in mediating fusion and apoptosis in bystander cells and to determine whether the two phenomena are related. FIV env interactions with target cells were blocked at the level of gp120 or gp41 and the effect of these on fusion and apoptosis studied. The role of FIV gp41 pre-TM region in fusion and apoptosis was also determined. Our findings support a role of FIV env in apoptotic loss of T cells and this phenomenon correlates with env-mediated fusion.
| Identifer | oai:union.ndltd.org:NCSU/oai:NCSU:etd-11042003-141554 |
| Date | 10 November 2003 |
| Creators | Garg, Himanshu |
| Contributors | Dr Frederick J Fuller, Dr Wayne A Tompkins, Dr Susan Tonkonogy, Dr Scott M Laster |
| Publisher | NCSU |
| Source Sets | North Carolina State University |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://www.lib.ncsu.edu/theses/available/etd-11042003-141554/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to NC State University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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