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Regulation of Proinflammatory Extracellular Vesicles from HIV Infected Cells by CBD

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dc.contributor.advisor Kashanchi, Fatah Cowen, Maria
dc.creator Cowen, Maria 2020-12-02 2021-01-27T13:58:51Z 2021-01-27T13:58:51Z
dc.description.abstract As of 2019, approximately 62% of the 37.9 million individuals infected with Human Immunodeficiency Virus type 1 (HIV-1) underwent combination antiretroviral therapy (cART) treatment, which includes a cocktail of inhibitory drugs for nearly all parts of the viral life cycle. The lack of an FDA approved viral transcription inhibitor allows for persistent non-processive transcription which results in the production of short non-coding RNAs (TAR and TAR-gag). Our lab and others have shown that these RNAs are released from the cell in extracellular vesicles (EVs), specifically exosomes, and can induce production of proinflammatory cytokines in recipient myeloid cells; a factor that may contribute to the neuroinflammation observed in HIV-1 infected individuals with HIV associated neurocognitive disorder (HAND). Here, we demonstrate that EVs released from HIV-1 infected macrophages with and without cART induce the production of proinflammatory cytokines from astrocytes via activation of TLR3 by EV cargo (TAR) and have identified three TAR inhibitor candidates to inhibit this mechanism. Furthermore, we show that CBD can lower secretion of EVs and their viral cargo potentially through intracellular viral transcription inhibition. Overall, this study demonstrates the therapeutic potential for CBD usage on lowering EV-mediated neuroinflammation seen in HAND. en_US
dc.language.iso en en_US
dc.subject Human immunodeficiency virus (HIV) en_US
dc.subject marijuana en_US
dc.subject Extracellular vesicles (EVs) en_US
dc.subject Cannabidiol (CBD) en_US
dc.subject Central nervous system (CNS) en_US
dc.subject HIV associated neurocognitive disorders (HAND) en_US
dc.title Regulation of Proinflammatory Extracellular Vesicles from HIV Infected Cells by CBD en_US
dc.type Thesis en_US Master of Science in Biology en_US Master's en_US Biology en_US George Mason University en_US

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