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

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 su...

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Autores principales: Dagur, Raghubendra Singh, Liao, Ke, Sil, Susmita, Niu, Fang, Sun, Zhiqiang, Lyubchenko, Yuri L., Peeples, Eric S., Hu, Guoku, Buch, Shilpa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6968593/
https://www.ncbi.nlm.nih.gov/pubmed/32002168
http://dx.doi.org/10.1080/20013078.2019.1703249
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author Dagur, Raghubendra Singh
Liao, Ke
Sil, Susmita
Niu, Fang
Sun, Zhiqiang
Lyubchenko, Yuri L.
Peeples, Eric S.
Hu, Guoku
Buch, Shilpa
author_facet Dagur, Raghubendra Singh
Liao, Ke
Sil, Susmita
Niu, Fang
Sun, Zhiqiang
Lyubchenko, Yuri L.
Peeples, Eric S.
Hu, Guoku
Buch, Shilpa
author_sort Dagur, Raghubendra Singh
collection PubMed
description 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.
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spelling pubmed-69685932020-01-30 Neuronal-derived extracellular vesicles are enriched in the brain and serum of HIV-1 transgenic rats Dagur, Raghubendra Singh Liao, Ke Sil, Susmita Niu, Fang Sun, Zhiqiang Lyubchenko, Yuri L. Peeples, Eric S. Hu, Guoku Buch, Shilpa J Extracell Vesicles Article 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. Taylor & Francis 2019-12-20 /pmc/articles/PMC6968593/ /pubmed/32002168 http://dx.doi.org/10.1080/20013078.2019.1703249 Text en © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of The International Society for Extracellular Vesicles. http://creativecommons.org/licenses/by-nc/4.0/ http://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Article
Dagur, Raghubendra Singh
Liao, Ke
Sil, Susmita
Niu, Fang
Sun, Zhiqiang
Lyubchenko, Yuri L.
Peeples, Eric S.
Hu, Guoku
Buch, Shilpa
Neuronal-derived extracellular vesicles are enriched in the brain and serum of HIV-1 transgenic rats
title Neuronal-derived extracellular vesicles are enriched in the brain and serum of HIV-1 transgenic rats
title_full Neuronal-derived extracellular vesicles are enriched in the brain and serum of HIV-1 transgenic rats
title_fullStr Neuronal-derived extracellular vesicles are enriched in the brain and serum of HIV-1 transgenic rats
title_full_unstemmed Neuronal-derived extracellular vesicles are enriched in the brain and serum of HIV-1 transgenic rats
title_short Neuronal-derived extracellular vesicles are enriched in the brain and serum of HIV-1 transgenic rats
title_sort neuronal-derived extracellular vesicles are enriched in the brain and serum of hiv-1 transgenic rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6968593/
https://www.ncbi.nlm.nih.gov/pubmed/32002168
http://dx.doi.org/10.1080/20013078.2019.1703249
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