Extracellular vesicles regulate gap junction-mediated intercellular communication and HIV-1 infection of human neural progenitor cells.

摘要: Abstract Human immunodeficiency virus-1 (HIV-1) has been shown to cross the blood-brain barrier and cause HIV-associated neurocognitive disorders (HAND) through a process that may involve direct or indirect interactions with central nervous system (CNS) cells alterations of amyloid β (Aβ) homeostasis. The present study focused on mechanisms HIV-1 infecting human neural progenitor (hNPCs) affecting NPC intercellular communications brain endothelial (HBMEC). Despite lack CD4 receptor, hNPCs were effectively infected by via mechanism involving chemokine receptors, CXCR4 CCR5. infection increased expression connexin-43 (Cx43), phosphorylated Cx43 (pCx43), pannexin 2 (Panx2) protein levels in hNPCs, suggesting gap-junction (GJ) channel communication. Indeed, functional GJ assay indicated an increase communication between HIV-infected non-infected HBMEC. We next analyzed impact HBMEC-derived extracellular vesicles (EVs) EVs carrying Aβ (EV-Aβ) Cx43, pCx43, Panx2 hNPCs. Exposure EV-Aβ resulted significant reduction pCx43 when compared EV controls. Interestingly, treatment significantly HIV-1-infected These results confirmed ATP release assay, which is indicator connexin hemichannel and/or functions. Overall, current demonstrates importance indicates HBMEC can be modulated as their cargo.