Submission Date

4-24-2017

Document Type

Paper- Restricted to Campus Access

Department

Biology

Adviser

Jennifer King

Committee Member

Kathryn Goddard

Committee Member

Peter Chi

Department Chair

Beth Bailey

Project Description

Anti-retroviral therapy (ART) has been successful in increasing the survival rate of HIV-infected patients, however the incidence of moderate cognitive impairment among patients remains high. The occurrence of HIV-Associated Neurocognitive Disorders (HAND) has been attributed to the persistence of latent HIV in resting T cells and macrophages, as well as chronic inflammation. Indirect neuronal damage occurs after HIV invasion of the brain despite neurons’ lack of CD4+ receptors necessary for HIV infection. Local microglia and leukocytes work together to eliminate the virus through the production of potentially neurotoxic chemokines. The phagocytic activity of microglia has been shown to be altered when exposed to HIV, but the cause of these changes is unknown. We hypothesize that pro-inflammatory chemokines released from microglia co-incubated with the HIV-1 Tat protein play a role in the change in functional activity of microglia, thereby damaging neurons. Phagocytic activity after exposure to HIV-1 Tat has previously been shown to be significantly decreased after a 24 hour incubation. Our goal is to better understand this functional change by upregulating the chemokine receptor CXCR3 on the surface of microglia cells, and on a more broad scale explore the effect of the HIV-1 protein Tat on BV-2 microglial cells in vitro. The phagocytic activity of BV-2 cells was quantified through confocal microscopy, transfection conducted using lipofection, and characterization of CXCR3 expression evaluated through western blotting. This study established methods for transfecting within the BV-2 cell line, and observed a preliminary decrease in CXCR3 expression in BV-2 cells co-incubated with HIV Tat. Our results give us further insight into the indirect factors that may play a role in neuronal death seen in HAND and neuroinflammation as a whole.

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