Modulation of GR transcriptional signalling by HIV-1 Vpr insights into regulation by progestins

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dc.contributor.advisorHapgood, Janet Pen_ZA
dc.contributor.advisorAvenant, Chanelen_ZA
dc.contributor.authorGrantham, N Jen_ZA
dc.date.accessioned2014-12-30T06:42:23Z
dc.date.available2014-12-30T06:42:23Z
dc.date.issued2012en_ZA
dc.descriptionIncludes bibliographical references.en_ZA
dc.description.abstractIt has been 30 years since HIV was first discovered, yet the molecular mechanisms whereby the virus mediates its pathogenic effects have not yet been completely elucidated. The glucocorticoid receptor (GR) is a ligand-activated host transcription factor, which mediates anti-inflammatory effects in response to stimulation with glucocorticoids (GC). One of the HIV-1 accessory proteins, Vpr, is highly immunosuppressive and contributes to suppression of the immune system thereby creating an environment favourable for viral proliferation. Vpr has been previously reported to act as a GR co-activator on glucocorticoid response element (GRE) containing promoters. Thus, the GR appears likely to play a role in HIV-1 pathogenesis. Contraceptive usage is also likely to affect HIV-1 pathogenesis as some hormonal contraceptives can bind to and activate the GR. Progesterone (P4) regulates the female reproductive system and the synthetic progestins medroxyprogesterone acetate (MPA) and norethisterone acetate (NET-A) are extensively used as injectable contraceptives. MPA has been shown to act as a partial or full GR agonist and recent evidence indicates that injectable MPA increases HIV-1 acquisition and transmission. The molecular mechanisms of this remain unclear, but may involve decreasing the thickness of the vaginal epithelium as well as actions via the GR that affect gene expression in the cervo-vaginal environment and/or elsewhere. This study aims to investigate the actions of GC's, P4, MPA and NET-A via the GR in the absence and presence of Vpr protein towards gaining some insight into the potential interplay between the host GR, contraceptive use, HIV-1 pathogenesis, and the mechanisms thereof.en_ZA
dc.identifier.apacitationGrantham, N. J. (2012). <i>Modulation of GR transcriptional signalling by HIV-1 Vpr insights into regulation by progestins</i>. (Thesis). University of Cape Town ,Faculty of Science ,Department of Molecular and Cell Biology. Retrieved from http://hdl.handle.net/11427/10520en_ZA
dc.identifier.chicagocitationGrantham, N J. <i>"Modulation of GR transcriptional signalling by HIV-1 Vpr insights into regulation by progestins."</i> Thesis., University of Cape Town ,Faculty of Science ,Department of Molecular and Cell Biology, 2012. http://hdl.handle.net/11427/10520en_ZA
dc.identifier.citationGrantham, N. 2012. Modulation of GR transcriptional signalling by HIV-1 Vpr insights into regulation by progestins. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Grantham, N J AB - It has been 30 years since HIV was first discovered, yet the molecular mechanisms whereby the virus mediates its pathogenic effects have not yet been completely elucidated. The glucocorticoid receptor (GR) is a ligand-activated host transcription factor, which mediates anti-inflammatory effects in response to stimulation with glucocorticoids (GC). One of the HIV-1 accessory proteins, Vpr, is highly immunosuppressive and contributes to suppression of the immune system thereby creating an environment favourable for viral proliferation. Vpr has been previously reported to act as a GR co-activator on glucocorticoid response element (GRE) containing promoters. Thus, the GR appears likely to play a role in HIV-1 pathogenesis. Contraceptive usage is also likely to affect HIV-1 pathogenesis as some hormonal contraceptives can bind to and activate the GR. Progesterone (P4) regulates the female reproductive system and the synthetic progestins medroxyprogesterone acetate (MPA) and norethisterone acetate (NET-A) are extensively used as injectable contraceptives. MPA has been shown to act as a partial or full GR agonist and recent evidence indicates that injectable MPA increases HIV-1 acquisition and transmission. The molecular mechanisms of this remain unclear, but may involve decreasing the thickness of the vaginal epithelium as well as actions via the GR that affect gene expression in the cervo-vaginal environment and/or elsewhere. This study aims to investigate the actions of GC's, P4, MPA and NET-A via the GR in the absence and presence of Vpr protein towards gaining some insight into the potential interplay between the host GR, contraceptive use, HIV-1 pathogenesis, and the mechanisms thereof. DA - 2012 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2012 T1 - Modulation of GR transcriptional signalling by HIV-1 Vpr insights into regulation by progestins TI - Modulation of GR transcriptional signalling by HIV-1 Vpr insights into regulation by progestins UR - http://hdl.handle.net/11427/10520 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/10520
dc.identifier.vancouvercitationGrantham NJ. Modulation of GR transcriptional signalling by HIV-1 Vpr insights into regulation by progestins. [Thesis]. University of Cape Town ,Faculty of Science ,Department of Molecular and Cell Biology, 2012 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/10520en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentDepartment of Molecular and Cell Biologyen_ZA
dc.publisher.facultyFaculty of Scienceen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherCell Biologyen_ZA
dc.titleModulation of GR transcriptional signalling by HIV-1 Vpr insights into regulation by progestinsen_ZA
dc.typeMaster Thesis
dc.type.qualificationlevelMasters
dc.type.qualificationnameMScen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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