TY - JOUR
T1 - HIV-1 Tat-Induced Astrocytic Extracellular Vesicle miR-7 Impairs Synaptic Architecture
AU - Hu, Guoku
AU - Niu, Fang
AU - Liao, Ke
AU - Periyasamy, Palsamy
AU - Sil, Susmita
AU - Liu, Jinxu
AU - Dravid, Shashank M.
AU - Buch, Shilpa
N1 - Funding Information:
This work was supported by the grants DA041751, DA043164, MH112848, DA040397, DA043138 (SB), and DA042704 and DA046831 (GH) from the National Institutes of Health. The support of the Nebraska Center for Substance Abuse Research is acknowledged. The project described was also supported by the NIH, National Institute of Mental Health, 2P30MH062261. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Publisher Copyright:
© 2019, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2020/9/1
Y1 - 2020/9/1
N2 - 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.].
AB - 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.].
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U2 - 10.1007/s11481-019-09869-8
DO - 10.1007/s11481-019-09869-8
M3 - Article
C2 - 31401755
AN - SCOPUS:85070403002
VL - 15
SP - 538
EP - 553
JO - Journal of NeuroImmune Pharmacology
JF - Journal of NeuroImmune Pharmacology
SN - 1557-1890
IS - 3
ER -