Cargando…
HIV-1 and opiates modulate miRNA profiles in extracellular vesicles
Opiate abuse increases the risk of HIV transmission and exacerbates HIV neuropathology by increasing inflammation and modulating immune cell function. Exosomal EVs(xEV) contain miRNAs that may be differentially expressed due to HIV infection or opiate abuse. Here we develop a preliminary exosomal-mi...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10666642/ https://www.ncbi.nlm.nih.gov/pubmed/38022533 http://dx.doi.org/10.3389/fimmu.2023.1259998 |
_version_ | 1785139088668491776 |
---|---|
author | Caobi, Allen Bonilla, Jesenia Gomez, Mario Andre, Mickensone Yndart, Adriana Fernandez-Lima, Francisco A. Nair, Madhavan P. Raymond, Andrea D. |
author_facet | Caobi, Allen Bonilla, Jesenia Gomez, Mario Andre, Mickensone Yndart, Adriana Fernandez-Lima, Francisco A. Nair, Madhavan P. Raymond, Andrea D. |
author_sort | Caobi, Allen |
collection | PubMed |
description | Opiate abuse increases the risk of HIV transmission and exacerbates HIV neuropathology by increasing inflammation and modulating immune cell function. Exosomal EVs(xEV) contain miRNAs that may be differentially expressed due to HIV infection or opiate abuse. Here we develop a preliminary exosomal-miRNA biomarker profile of HIV-infected PBMCs in the context of opiate use. PBMCs infected with HIV were treated with increasing dosages of morphine for 72 hours, the culture supernatants were collected, and the exosomes isolated using differential centrifugation. Exosomal miRNAs were extracted, expression levels determined via Nanostring multiplexed microRNA arrays, and analyzed with Webgestalt. The effect of the exosomes on neuronal function was determined by measuring calcium. Preliminary findings show that HIV-1 infection altered the miRNA profile of PBMC-derived EVs concurrently with opiate exposure. MicroRNA, hsa-miR-1246 was up-regulated 12-fold in the presence of morphine, relative to uninfected control. PBMCs infected with HIV-1 MN, an X4-tropic HIV-1 strain and exposed to morphine, displayed a trend which suggests potential synergistic effects between HIV-1 infection and morphine exposure promoting an increase in viral replication. Dose-dependent differences were observed in miRNA expression as a result of opiate exposure. The xEVs derived from PBMCs exposed to morphine or HIV modulated neuronal cell function. SH-SY5Y cells, treated with xEVs derived from ART-treated PBMCs, exhibited increased viability while for SH-SY5Ys exposed to xEVs derived from HIV-1 infected PBMCs viability was decreased compared to the untreated control. Exposing SH-SY5Y to xEVs derived from HIV-infected PBMCs resulted in significant decrease in calcium signaling, relative to treatment with xEVs derived from uninfected PBMCs. Overall, HIV-1 and morphine induced differential miRNA expression in PBMC-derived exosomes, potentially identifying mechanisms of action or novel therapeutic targets involved in opiate use disorder, HIV neuropathology, TNF signaling pathway, NF-κB signaling pathway, autophagy, and apoptosis in context of HIV infection. |
format | Online Article Text |
id | pubmed-10666642 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-106666422023-01-01 HIV-1 and opiates modulate miRNA profiles in extracellular vesicles Caobi, Allen Bonilla, Jesenia Gomez, Mario Andre, Mickensone Yndart, Adriana Fernandez-Lima, Francisco A. Nair, Madhavan P. Raymond, Andrea D. Front Immunol Immunology Opiate abuse increases the risk of HIV transmission and exacerbates HIV neuropathology by increasing inflammation and modulating immune cell function. Exosomal EVs(xEV) contain miRNAs that may be differentially expressed due to HIV infection or opiate abuse. Here we develop a preliminary exosomal-miRNA biomarker profile of HIV-infected PBMCs in the context of opiate use. PBMCs infected with HIV were treated with increasing dosages of morphine for 72 hours, the culture supernatants were collected, and the exosomes isolated using differential centrifugation. Exosomal miRNAs were extracted, expression levels determined via Nanostring multiplexed microRNA arrays, and analyzed with Webgestalt. The effect of the exosomes on neuronal function was determined by measuring calcium. Preliminary findings show that HIV-1 infection altered the miRNA profile of PBMC-derived EVs concurrently with opiate exposure. MicroRNA, hsa-miR-1246 was up-regulated 12-fold in the presence of morphine, relative to uninfected control. PBMCs infected with HIV-1 MN, an X4-tropic HIV-1 strain and exposed to morphine, displayed a trend which suggests potential synergistic effects between HIV-1 infection and morphine exposure promoting an increase in viral replication. Dose-dependent differences were observed in miRNA expression as a result of opiate exposure. The xEVs derived from PBMCs exposed to morphine or HIV modulated neuronal cell function. SH-SY5Y cells, treated with xEVs derived from ART-treated PBMCs, exhibited increased viability while for SH-SY5Ys exposed to xEVs derived from HIV-1 infected PBMCs viability was decreased compared to the untreated control. Exposing SH-SY5Y to xEVs derived from HIV-infected PBMCs resulted in significant decrease in calcium signaling, relative to treatment with xEVs derived from uninfected PBMCs. Overall, HIV-1 and morphine induced differential miRNA expression in PBMC-derived exosomes, potentially identifying mechanisms of action or novel therapeutic targets involved in opiate use disorder, HIV neuropathology, TNF signaling pathway, NF-κB signaling pathway, autophagy, and apoptosis in context of HIV infection. Frontiers Media S.A. 2023-11-09 /pmc/articles/PMC10666642/ /pubmed/38022533 http://dx.doi.org/10.3389/fimmu.2023.1259998 Text en Copyright © 2023 Caobi, Bonilla, Gomez, Andre, Yndart, Fernandez-Lima, Nair and Raymond https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Caobi, Allen Bonilla, Jesenia Gomez, Mario Andre, Mickensone Yndart, Adriana Fernandez-Lima, Francisco A. Nair, Madhavan P. Raymond, Andrea D. HIV-1 and opiates modulate miRNA profiles in extracellular vesicles |
title | HIV-1 and opiates modulate miRNA profiles in extracellular vesicles |
title_full | HIV-1 and opiates modulate miRNA profiles in extracellular vesicles |
title_fullStr | HIV-1 and opiates modulate miRNA profiles in extracellular vesicles |
title_full_unstemmed | HIV-1 and opiates modulate miRNA profiles in extracellular vesicles |
title_short | HIV-1 and opiates modulate miRNA profiles in extracellular vesicles |
title_sort | hiv-1 and opiates modulate mirna profiles in extracellular vesicles |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10666642/ https://www.ncbi.nlm.nih.gov/pubmed/38022533 http://dx.doi.org/10.3389/fimmu.2023.1259998 |
work_keys_str_mv | AT caobiallen hiv1andopiatesmodulatemirnaprofilesinextracellularvesicles AT bonillajesenia hiv1andopiatesmodulatemirnaprofilesinextracellularvesicles AT gomezmario hiv1andopiatesmodulatemirnaprofilesinextracellularvesicles AT andremickensone hiv1andopiatesmodulatemirnaprofilesinextracellularvesicles AT yndartadriana hiv1andopiatesmodulatemirnaprofilesinextracellularvesicles AT fernandezlimafranciscoa hiv1andopiatesmodulatemirnaprofilesinextracellularvesicles AT nairmadhavanp hiv1andopiatesmodulatemirnaprofilesinextracellularvesicles AT raymondandread hiv1andopiatesmodulatemirnaprofilesinextracellularvesicles |