Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

Delineating the Role of SIV Vpr and Vpx on Dendritic Cells, NK Cells, and Immunity

Baglyas, Krisztina (2008) Delineating the Role of SIV Vpr and Vpx on Dendritic Cells, NK Cells, and Immunity. Master's Thesis, University of Pittsburgh. (Unpublished)

[img]
Preview
PDF
Primary Text

Download (3MB) | Preview

Abstract

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.


Share

Citation/Export:
Social Networking:
Share |

Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Baglyas, Krisztinakrisztinabaglyas@gmail.com
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairAyyavoo, Velpandivelpandi@pitt.eduVELPANDI
Committee MemberMurphey-Corb, Michaelmcorb@pitt.eduMCORB
Committee MemberReinhart, Toddreinhart@pitt.eduREINHART
Date: 28 September 2008
Date Type: Completion
Defense Date: 4 June 2008
Approval Date: 28 September 2008
Submission Date: 13 June 2008
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: Dendritic Cells; HIV; Natural Killer Cells; SIV; Vpr; Vpx
Other ID: http://etd.library.pitt.edu/ETD/available/etd-06132008-131704/, etd-06132008-131704
Date Deposited: 10 Nov 2011 19:47
Last Modified: 15 Nov 2016 13:44
URI: http://d-scholarship.pitt.edu/id/eprint/8096

Metrics

Monthly Views for the past 3 years

Plum Analytics


Actions (login required)

View Item View Item