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Elevated Abundance, Size, and MicroRNA Content of Plasma Extracellular Vesicles in Viremic HIV-1+ Patients: Correlations With Known Markers of Disease Progression
Because of factors only partly understood, the generalized elevated immune activation and inflammation characterizing HIV-1–infected patients are corrected incompletely with antiretroviral therapy (ART). Extracellular vesicles (EVs) including exosomes and microvesicles released by several cell types...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
JAIDS Journal of Acquired Immune Deficiency Syndromes
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4627170/ https://www.ncbi.nlm.nih.gov/pubmed/26181817 http://dx.doi.org/10.1097/QAI.0000000000000756 |
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author | Hubert, Audrey Subra, Caroline Jenabian, Mohammad-Ali Tremblay Labrecque, Pierre-François Tremblay, Cécile Laffont, Benoit Provost, Patrick Routy, Jean-Pierre Gilbert, Caroline |
author_facet | Hubert, Audrey Subra, Caroline Jenabian, Mohammad-Ali Tremblay Labrecque, Pierre-François Tremblay, Cécile Laffont, Benoit Provost, Patrick Routy, Jean-Pierre Gilbert, Caroline |
author_sort | Hubert, Audrey |
collection | PubMed |
description | Because of factors only partly understood, the generalized elevated immune activation and inflammation characterizing HIV-1–infected patients are corrected incompletely with antiretroviral therapy (ART). Extracellular vesicles (EVs) including exosomes and microvesicles released by several cell types may contribute to immune activation and dysfunction. EV size, abundance, and content appear to differ according to infection phase, disease progression, and ART. METHODS: We examined whether the size of EVs and the abundance of exosomes in plasma are associated with cell and tissue activation as well as with viral production. Acetylcholinesterase-bearing (AChE+) exosomes in plasma were quantified using an AChE assay. EV size was analyzed using dynamic light scattering. Proteins and microRNAs present in EVs were detected by Western blot and real-time polymerase chain reaction, respectively. RESULTS: Exosomes were found more abundant in the plasma of ART-naive patients. EV size was larger in ART-naive than in ART-suppressed patients, elite controllers, or healthy control subjects. Both exosome abundance and EV sizes were inversely correlated with CD4/CD8 T-cell ratio and neutrophil, platelet, and CD4 T-cell counts and positively correlated with CD8 T-cell counts. A negative correlation was found between CD4 T-cell nadir and exosome abundance, but not EV size. Levels of miR-155 and miR-223 but not miR-92 were strongly correlated negatively with EV abundance and size in ART-naive patients. CONCLUSIONS: Monitoring of circulating EVs and EV-borne microRNA is possible and may provide new insight into HIV-1 pathogenesis, disease progression, and the associated inflammatory state, as well as the efficacy of ART and the treatments intended to reduce immune activation. |
format | Online Article Text |
id | pubmed-4627170 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | JAIDS Journal of Acquired Immune Deficiency Syndromes |
record_format | MEDLINE/PubMed |
spelling | pubmed-46271702015-11-20 Elevated Abundance, Size, and MicroRNA Content of Plasma Extracellular Vesicles in Viremic HIV-1+ Patients: Correlations With Known Markers of Disease Progression Hubert, Audrey Subra, Caroline Jenabian, Mohammad-Ali Tremblay Labrecque, Pierre-François Tremblay, Cécile Laffont, Benoit Provost, Patrick Routy, Jean-Pierre Gilbert, Caroline J Acquir Immune Defic Syndr Basic and Translational Science Because of factors only partly understood, the generalized elevated immune activation and inflammation characterizing HIV-1–infected patients are corrected incompletely with antiretroviral therapy (ART). Extracellular vesicles (EVs) including exosomes and microvesicles released by several cell types may contribute to immune activation and dysfunction. EV size, abundance, and content appear to differ according to infection phase, disease progression, and ART. METHODS: We examined whether the size of EVs and the abundance of exosomes in plasma are associated with cell and tissue activation as well as with viral production. Acetylcholinesterase-bearing (AChE+) exosomes in plasma were quantified using an AChE assay. EV size was analyzed using dynamic light scattering. Proteins and microRNAs present in EVs were detected by Western blot and real-time polymerase chain reaction, respectively. RESULTS: Exosomes were found more abundant in the plasma of ART-naive patients. EV size was larger in ART-naive than in ART-suppressed patients, elite controllers, or healthy control subjects. Both exosome abundance and EV sizes were inversely correlated with CD4/CD8 T-cell ratio and neutrophil, platelet, and CD4 T-cell counts and positively correlated with CD8 T-cell counts. A negative correlation was found between CD4 T-cell nadir and exosome abundance, but not EV size. Levels of miR-155 and miR-223 but not miR-92 were strongly correlated negatively with EV abundance and size in ART-naive patients. CONCLUSIONS: Monitoring of circulating EVs and EV-borne microRNA is possible and may provide new insight into HIV-1 pathogenesis, disease progression, and the associated inflammatory state, as well as the efficacy of ART and the treatments intended to reduce immune activation. JAIDS Journal of Acquired Immune Deficiency Syndromes 2015-11-01 2015-10-15 /pmc/articles/PMC4627170/ /pubmed/26181817 http://dx.doi.org/10.1097/QAI.0000000000000756 Text en Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially. |
spellingShingle | Basic and Translational Science Hubert, Audrey Subra, Caroline Jenabian, Mohammad-Ali Tremblay Labrecque, Pierre-François Tremblay, Cécile Laffont, Benoit Provost, Patrick Routy, Jean-Pierre Gilbert, Caroline Elevated Abundance, Size, and MicroRNA Content of Plasma Extracellular Vesicles in Viremic HIV-1+ Patients: Correlations With Known Markers of Disease Progression |
title | Elevated Abundance, Size, and MicroRNA Content of Plasma Extracellular Vesicles in Viremic HIV-1+ Patients: Correlations With Known Markers of Disease Progression |
title_full | Elevated Abundance, Size, and MicroRNA Content of Plasma Extracellular Vesicles in Viremic HIV-1+ Patients: Correlations With Known Markers of Disease Progression |
title_fullStr | Elevated Abundance, Size, and MicroRNA Content of Plasma Extracellular Vesicles in Viremic HIV-1+ Patients: Correlations With Known Markers of Disease Progression |
title_full_unstemmed | Elevated Abundance, Size, and MicroRNA Content of Plasma Extracellular Vesicles in Viremic HIV-1+ Patients: Correlations With Known Markers of Disease Progression |
title_short | Elevated Abundance, Size, and MicroRNA Content of Plasma Extracellular Vesicles in Viremic HIV-1+ Patients: Correlations With Known Markers of Disease Progression |
title_sort | elevated abundance, size, and microrna content of plasma extracellular vesicles in viremic hiv-1+ patients: correlations with known markers of disease progression |
topic | Basic and Translational Science |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4627170/ https://www.ncbi.nlm.nih.gov/pubmed/26181817 http://dx.doi.org/10.1097/QAI.0000000000000756 |
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