Wheeler, Elizabeth Dale Ann
(2005)
DETECTION OF HIV-1 VIRAL PROTEIN R IN HIV ENCEPHALITIC BRAIN TISSUE.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
HIV-1 Associated Dementia (HAD), the most severe neurological complication associated with HIV-1 infection, is commonly characterized by inflammation of the brain and neuronal degeneration, known as HIV Encephalitis (HIVE). HIVE develops in 20-30% of patients infected with HIV, which means that 9.5 million people are affected by HIVE throughout the world. While the introduction of highly active antiretroviral therapy (HAART) has decreased the incidence of severe late-stage HAD, the prevalence of its precursor HIVE is actually rising. Several HIV-1 viral proteins have been shown using in vitro models to have a role in the neurotoxic effects causing the neurodegeneration seen during HIVE. HIV-1 Viral Protein R (Vpr), a virion associated gene product which induces apoptosis in non-proliferating cells including neurons, is thought to contribute to the neuropathogenesis associated with HIVE. Previous studies have shown the presence of detectable levels of Vpr in the cerebrospinal fluid of HIV-1 infected patients. Extracellular Vpr released from HIV-1 infected macrophages has also been shown to be capable of transducing into cells not normally infected by HIV-1, causing death of these bystander cells. Additionally, Vpr has been shown in vitro to be able to induce apoptosis in human neurons. Although current research suggests that Vpr plays a significant role in neuropathogenesis, no work has been done yet in vivo to show the presence of Vpr in the brain tissue of HIVE patients. Using a panel of eight HIVE and four HIV seronegative patient brain tissue sections, I performed immunohistochemistry staining for Vpr, p24, and brain cell specific markers. Results indicate that Vpr was present in detectable amounts in both the basal ganglia and frontal cortex of all eight HIVE brain tissue samples tested. Double label immunohistochemistry was performed using antibodies specific for astrocytes macrophages and neurons. I detected the presence of Vpr in the macrophages and neurons, but not in the astrocytes, of HIVE patients. The results of this study strongly support the role of Vpr in the neuropathogenesis seen during HIVE. Further studies based on these findings could lead to the development of effective therapeutic treatments necessary to reduce, and possibly prevent, this public health epidemic.
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Details
| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
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| ETD Committee: |
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| Date: |
13 September 2005 |
| Date Type: |
Completion |
| Defense Date: |
28 June 2005 |
| Approval Date: |
13 September 2005 |
| Submission Date: |
5 July 2005 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Public Health > Infectious Diseases and Microbiology |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
encephalitis; HIV; immunohistochemistry; Vpr |
| Other ID: |
http://etd.library.pitt.edu/ETD/available/etd-07052005-140605/, etd-07052005-140605 |
| Date Deposited: |
10 Nov 2011 19:49 |
| Last Modified: |
15 Nov 2016 13:45 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/8266 |
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