Understanding the Mechanism by which Sulforaphane Promotes SAMHD1 Activation to Protect Macrophages Against HIV Infection

Simple item page
dc.contributor.advisorSingh, Vir
dc.contributor.authorFazzari, Vincent A. '22
dc.contributor.committeememberSharifi, H. John
dc.contributor.committeememberMalik, Meenakshi
dc.contributor.committeememberShi, Binshan
dc.date.accessioned2023-04-18T18:59:12Z
dc.date.available2023-04-18T18:59:12Z
dc.date.issued2022-08
dc.descriptionClick on the Resource Link to find this item in the ACPHS Library catalog.
dc.description.abstractThe human immunodeficiency virus (HIV) is the causative agent of acquired immunodeficiency syndrome (AIDS). To date, HIV/AIDS has killed an estimated 40 million people. There is no cure, no vaccine, and current therapies are burdened with high cost and toxicity. Therefore, further study of HIV is necessary. Sulforaphane (SFN), a compound found in cruciferous vegetables, was shown to block HIV infection of macrophages through activation of the transcription factor Nrf2. Follow up, unpublished, work by H. John Sharifi, PhD and Dakota Paine, M.S. found that SFN promotes the absence of an inhibitory phosphate from the antiviral protein SAMHD1. The exact mechanism of unphosphorylated SAMHD1 by SFN is unclear. The goal of this work was to uncover potential ways that SFN can yield unphosphorylated SAMHD1. Our central hypothesis is that SFN, acting through Nrf2, upregulates p21 and drives SAMHD1 into the nucleus to promote SAMHD1 dephosphorylation and protection against HIV. This hypothesis is based on an observation by Dr. Sharifi and Mr. Paine that SFN upregulates p21, also known as cyclin-dependent kinase inhibitor 1, in primary macrophages. p21 is a cell cycle control protein that has been previously shown to inhibit SAMHD1 phosphorylation. This hypothesis is additionally based on work showing that SAMHD1 accumulates in the cytosol under oxidizing conditions and that SFN promotes reducing conditions. This hypothesis was tested to determine the influence on SAMHD1 phosphorylation. Here, we first confirmed that SAMHD1 is required for the antiviral effect of SFN. We then established that p21 levels do not necessarily connect SFN to unphosphorylated SAMHD1. We further show that SFN does not change the intracellular location of SAMHD1.
dc.description.degreeMS in Molecular Biosciences
dc.description.urihttps://acphs.on.worldcat.org/oclc/1370948209
dc.format.extent65 pages
dc.identifier.citationFazzari V. Understanding the mechanism by which sulforaphane promotes SAMHD1 activation to protect macrophages against HIV infection [thesis]. Ann Arbor (MI): Proquest LLC; 2022. 65 p.
dc.identifier.urihttps://hdl.handle.net/20.500.14303/26
dc.languageen
dc.publisherProQuest LLC
dc.relation.ispartofAlbany College of Pharmacy and Health Sciences Theses
dc.rightsThis Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). http://rightsstatements.org/vocab/InC/1.0/
dc.subjectHIV Infections
dc.subjectSulfoxides
dc.subjectSAM Domain and HD Domain-Containing Protein 1
dc.subjectMacrophages
dc.titleUnderstanding the Mechanism by which Sulforaphane Promotes SAMHD1 Activation to Protect Macrophages Against HIV Infection
dc.typeThesis
local.departmentprogramDepartment of Life Sciences
local.departmentprogramMSMB MS in Molecular Biosciences
Files
Collections
Masters of Science in Molecular Biosciences Theses