UCLA Library

Abstract: HIV-1 is the most common Human Immunodeficiency Virus. It attacks the body’s immune system and kills CD4 cells. Antiretroviraltherapies (ART) have been developed to combat HIV-1, however HIV-1 persists is due to reservoirs of latent virus in the body. Inaddition, up to 50% of patients on ART will develop motor/memory impairments later in life withHIV-1 associated neurocognitive diseases (HAND)(Rai2020). Previous experiments have found that cells in the central nervous system (CNS), such as astrocytes andmicroglia, are potential reservoirs for latent HIV in the body and could contribute to HAND (Wallet 2019). However, the results are conflicting as to which cell types can be infected. Targeting these reservoirs in vivo is challenging due to the blood-brain barrier preventing drugs from reaching these reservoirs (Wallet 2019). In the lab, the mechanisms of HIV infection can be studied using the replication competent strain, AD8 or dEnv, a virus pseudotyped with an envelope from Vesicular Stomatitis Virus (VSV) that has a different entry mechanism to infect cells, but cannot replicate (Hastie 2013). In my research project, I hypothesize that AD8 will selectively infect microglial cells. Microglial cells infected with either AD8 or dEnv will then lead to reactive changes in astrocytes and neurons leading to the pathology seen in HAND. In this study, the production of human pluripotent stem cell (hPSC) derived microglia, neurons, and astrocytes was optimized using immuno histochemistry (IHC) and qPCR. The effects of HIV infectionon microglia proliferation and migration was determined. After successful  differentiation of neural progenit or cells (NPCs) to neurons and astrocytes, atri-culture system was then optimized to study the indirect effects of HIV infection, via the consequence of infected microglia on other cells in the CNS.