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Improving the 3D-CNS Organoid Model to Study Human Immunodeficiency Virus (HIV-1) Neuropathogenesis: Inclusion of the Blood-Brain Barrier

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 (Unpublished)

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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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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Tom, Aiyana-MeiAIT11@pitt.eduait11
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairAyyavoo, Velpandivelpandi@pitt.eduvelpandi
Committee MemberMartinson, Jeremyjmartins@pitt.edujmartins
Committee MemberKlimstra, William Brownklimstra@pitt.eduklimstra
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


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