Neuronal‐derived extracellular vesicles are enriched in the brain and serum of HIV‐1 transgenic rats

Abstract

ABSTRACT Despite the efficacy of combination antiretroviral therapy (ART) in controlling human immunodeficiency virus (HIV‐1) replication, cytotoxic viral proteins such as HIV‐1 transactivator of transcription (Tat) persist in tissues such as the brain. Although HIV‐1 does not infect neuronal cells, it is susceptible to viral Tat protein‐mediated toxicity, leading to neuroinflammation that underlies HIV‐associated neurocognitive disorders (HAND). Given the role of extracellular vesicles (EVs) in both cellular homoeostasis and under pathological conditions, we sought to investigate the alterations in the quantity of neuronal‐derived EVs in the brain – as defined by the presence of cell adhesion molecule L1 (L1CAM) and to evaluate the presence of L1CAM + EVs in the peripheral circulation of HIV‐1 transgenic (HIV‐1 Tg) rats. The primary goal of this study was to investigate the effect of long‐term exposure of HIV‐1 viral proteins on the release of neuronal EVs in the brain and their transfer in the systemic compartment. Brain and serum EVs were isolated from both wild type and HIV‐1 Tg rats using differential ultracentrifugation with further purification using the Optiprep gradient method. The subpopulation of neuronal EVs was further enriched using immunoprecipitation. The current findings demonstrated increased presence of L1CAM + neuronal‐derived EVs both in the brain and serum of HIV‐1 Tg rats.