Tom, Aiyana-Mei
(2023)
Improving the 3D-CNS Organoid Model to Study Human Immunodeficiency Virus (HIV-1) Neuropathogenesis: Inclusion of the Blood-Brain Barrier.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
The elimination of human immunodeficiency virus (HIV-1) from the body presents a challenge, even with the advent of effective antiretroviral therapy (ART). Although ART successfully manages HIV-1 infection, it does not completely eliminate the viral reservoir from the body. Antiviral drugs are inefficient in crossing the blood-brain barrier (BBB) and are thus unable to suppress the viral reservoir of HIV-1 in the central nervous system (CNS). The blood-brain barrier is a critically important protective barrier that is involved in providing essential biologic, physiologic, and immunologic separation between the central nervous system (CNS) and the periphery. HIV-1-infected monocytes from the periphery cross the BBB and establish themselves in the CNS as perivascular macrophages within the first 14 days of HIV-1 infection, yet the exact method of transmigration is still unknown. Our laboratory is developing an in vitro HIV-1-CNS model to understand the role of different cell lineages including blood brain barrier endothelial cells. To determine how the HIV-1 target cell types that cross the BBB, and establish infection in CNS, first I assessed the viral replication kinetics using THP-1 monocytes and primary human monocytes. I then infected target cells with HIV-1-reporter viruses, allowed the cells to differentiate and determined the amount of infectious virus, p24 and RNA, both pre- and post-infection. I then determined how HIV-1-infected monocytes and macrophages cross the BBB and establish infection in the brain to better develop future antiviral drugs.
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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Unpublished |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: |
10 April 2023 |
| Defense Date: |
21 April 2023 |
| Approval Date: |
11 May 2023 |
| Submission Date: |
28 April 2023 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
67 |
| 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: |
- |
| Date Deposited: |
11 May 2023 16:40 |
| Last Modified: |
11 May 2023 16:40 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/44820 |
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