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

Raghubendra Singh Dagur, Ke Liao, Susmita Sil, Fang Niu, Zhiqiang Sun, Yuri L. Lyubchenko, Eric S. Peeples, Guoku Hu, Shilpa Buch

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number1703249
JournalJournal of Extracellular Vesicles
Volume9
Issue number1
DOIs
StatePublished - Jan 1 2020

Keywords

  • Extracellular vesicles
  • HIV-1
  • brain EVs
  • neuronal EVs
  • serum EVs

ASJC Scopus subject areas

  • Histology
  • Cell Biology

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