HIV-1 Tat-Induced Astrocytic Extracellular Vesicle miR-7 Impairs Synaptic Architecture

Guoku Hu, Fang Niu, Ke Liao, Palsamy Periyasamy, Susmita Sil, Jinxu Liu, Shashank M. Dravid, Shilpa Buch

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Although combination antiretroviral therapy (cART) has improved the health of millions of those living with HIV-1 (Human Immunodeficiency Virus, Type 1), the penetration into the central nervous system (CNS) of many such therapies is limited, thereby resulting in residual neurocognitive impairment commonly referred to as NeuroHIV. Additionally, while cART has successfully suppressed peripheral viremia, cytotoxicity associated with the presence of viral Transactivator of transcription (Tat) protein in tissues such as the brain, remains a significant concern. Our previous study has demonstrated that both HIV-1 Tat as well as opiates such as morphine, can directly induce synaptic alterations via independent pathways. Herein, we demonstrate that exposure of astrocytes to HIV-1 protein Tat mediates the induction and release of extracellular vesicle (EV) microRNA-7 (miR-7) that is taken up by neurons, leading in turn, to downregulation of neuronal neuroligin 2 (NLGN2) and ultimately to synaptic alterations. More importantly, we report that these impairments could be reversed by pretreatment of neurons with a neurotrophic factor platelet-derived growth factor-CC (PDGF-CC). [Figure not available: see fulltext.].

Original languageEnglish (US)
JournalJournal of Neuroimmune Pharmacology
DOIs
StateAccepted/In press - Jan 1 2019

Keywords

  • Extracellular vesicles
  • HIV-1 tat
  • Neuroligin
  • PDGF
  • Synapse
  • miRNA

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Immunology and Allergy
  • Immunology
  • Pharmacology

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