Studies of viral accessory genes have progressed in order to understand pathogenesis and develop effective therapeutics and vaccines. For human immunodeficiency virus type-1 (HIV-1), one such gene receiving special focus is vpr. Vpr has been implicated in dysregulation of host cellular events (including cell cycle arrest and apoptosis), infection of non-dividing cells, and increased viral replication in infected T cells. In simian immunodeficiency virus (SIV), a similar gene is seen in a slightly different form, including vpr as well as a duplicate, vpx. In SIV, these two genes have been shown to split the functions of HIV-1 vpr. In order to use SIV as a model for HIV-1, it must be determined which SIV gene is responsible for mediation of different functional effects.
HIV-1 vpr has been shown to downmodulate surface markers on dendritic cells and alter cytokine environments in vivo. Studies have shown that HIV-1 vpr pushes natural killer cells into anergy, rendering them non-functional. Results presented in this study indicate SIV infection also results in these effects, but responsibility for these effects is split between SIV vpr and vpx. The vpx gene appears to play a role in downmodulation of surface receptors on dendritic cells and changes the cytokine environment within the dendritic cells. The vpr gene, however, appears to be responsible for decreased functionality of NK cells, leading to a non-functional anergic state. These findings suggest SIV vpx and vpr cause similar effects compared to HIV-1 vpr and, as expected, the SIV genes split the functions of their HIV-1 homolog.
Statement of Public Health Relevance: HIV infection and disease is a growing epidemic and it has become increasingly apparent that in vitro studies are not sufficient to provide the data needed to create an effective vaccine. Because vaccine research cannot be performed on human subjects, the best mode for transition would be a shift to in vivo studies on non-human primates using SIV as a model for HIV-1 infection and disease. Before this can be adopted, it will be necessary to show HIV-1 and SIV have similar effects in vitro on immune cells and can be used interchangeably.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-06132008-131704 |
| Date | 28 September 2008 |
| Creators | Baglyas, Krisztina |
| Contributors | Michael Murphey-Corb, Velpandi Ayyavoo, Todd Reinhart |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-06132008-131704/ |
| Rights | restricted, 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 University of Pittsburgh 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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