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Interleukin-1β Triggers p53-Mediated Downmodulation of CCR5 and HIV-1 Entry in Macrophages through MicroRNAs 103 and 107

Macrophages are a target of human immunodeficiency virus type 1 (HIV-1) and may serve as a viral reservoir during antiretroviral therapy (ART). Their susceptibility to HIV-1 infection is subject to variations from permissiveness to resistance depending on their origin, tissue localization, and polar...

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Autores principales: Lodge, Robert, Bellini, Nicolas, Laporte, Mélanie, Salahuddin, Syim, Routy, Jean-Pierre, Ancuta, Petronela, Costiniuk, Cecilia T., Jenabian, Mohammad-Ali, Cohen, Éric A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527731/
https://www.ncbi.nlm.nih.gov/pubmed/32994328
http://dx.doi.org/10.1128/mBio.02314-20
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author Lodge, Robert
Bellini, Nicolas
Laporte, Mélanie
Salahuddin, Syim
Routy, Jean-Pierre
Ancuta, Petronela
Costiniuk, Cecilia T.
Jenabian, Mohammad-Ali
Cohen, Éric A.
author_facet Lodge, Robert
Bellini, Nicolas
Laporte, Mélanie
Salahuddin, Syim
Routy, Jean-Pierre
Ancuta, Petronela
Costiniuk, Cecilia T.
Jenabian, Mohammad-Ali
Cohen, Éric A.
author_sort Lodge, Robert
collection PubMed
description Macrophages are a target of human immunodeficiency virus type 1 (HIV-1) and may serve as a viral reservoir during antiretroviral therapy (ART). Their susceptibility to HIV-1 infection is subject to variations from permissiveness to resistance depending on their origin, tissue localization, and polarization profile. This is in part due to the expression of regulatory microRNAs. Here, we identify two microRNA paralogs, microRNA 103 (miR-103) and miR-107, as regulators of CCR5 expression that are upregulated in noninfected bystander cells of HIV-1-infected-monocyte-derived macrophage (MDM) cultures. Transfection of microRNA 103 mimics in MDMs reduced CCR5 expression levels and inhibited CCR5-dependent HIV-1 entry, whereas the corresponding antagomirs enhanced virus spread in HIV-infected MDMs. Treatment of MDMs with interleukin-1β (IL-1β) enhanced microRNA 103 expression, a condition that we found contributed to the reduction of CCR5 mRNA in IL-1β-exposed MDMs. Interestingly, we show that the induction of miR-103/107 expression is part of a tumor suppressor p53 response triggered by secreted IL-1β that renders macrophages refractory to HIV-1 entry. In a more physiological context, the levels of microRNAs 103 and 107 were found enriched in tissue-resident colon macrophages of healthy donors and alveolar macrophages of individuals under antiretroviral therapy, conceivably contributing to their relative resistance to HIV-1 infection. Overall, these findings highlight the role of p53 in enforcing proinflammatory antiviral responses in macrophages, at least in part, through miR-103/107-mediated downmodulation of CCR5 expression and HIV-1 entry.
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spelling pubmed-75277312020-10-19 Interleukin-1β Triggers p53-Mediated Downmodulation of CCR5 and HIV-1 Entry in Macrophages through MicroRNAs 103 and 107 Lodge, Robert Bellini, Nicolas Laporte, Mélanie Salahuddin, Syim Routy, Jean-Pierre Ancuta, Petronela Costiniuk, Cecilia T. Jenabian, Mohammad-Ali Cohen, Éric A. mBio Research Article Macrophages are a target of human immunodeficiency virus type 1 (HIV-1) and may serve as a viral reservoir during antiretroviral therapy (ART). Their susceptibility to HIV-1 infection is subject to variations from permissiveness to resistance depending on their origin, tissue localization, and polarization profile. This is in part due to the expression of regulatory microRNAs. Here, we identify two microRNA paralogs, microRNA 103 (miR-103) and miR-107, as regulators of CCR5 expression that are upregulated in noninfected bystander cells of HIV-1-infected-monocyte-derived macrophage (MDM) cultures. Transfection of microRNA 103 mimics in MDMs reduced CCR5 expression levels and inhibited CCR5-dependent HIV-1 entry, whereas the corresponding antagomirs enhanced virus spread in HIV-infected MDMs. Treatment of MDMs with interleukin-1β (IL-1β) enhanced microRNA 103 expression, a condition that we found contributed to the reduction of CCR5 mRNA in IL-1β-exposed MDMs. Interestingly, we show that the induction of miR-103/107 expression is part of a tumor suppressor p53 response triggered by secreted IL-1β that renders macrophages refractory to HIV-1 entry. In a more physiological context, the levels of microRNAs 103 and 107 were found enriched in tissue-resident colon macrophages of healthy donors and alveolar macrophages of individuals under antiretroviral therapy, conceivably contributing to their relative resistance to HIV-1 infection. Overall, these findings highlight the role of p53 in enforcing proinflammatory antiviral responses in macrophages, at least in part, through miR-103/107-mediated downmodulation of CCR5 expression and HIV-1 entry. American Society for Microbiology 2020-09-29 /pmc/articles/PMC7527731/ /pubmed/32994328 http://dx.doi.org/10.1128/mBio.02314-20 Text en Copyright © 2020 Lodge et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Lodge, Robert
Bellini, Nicolas
Laporte, Mélanie
Salahuddin, Syim
Routy, Jean-Pierre
Ancuta, Petronela
Costiniuk, Cecilia T.
Jenabian, Mohammad-Ali
Cohen, Éric A.
Interleukin-1β Triggers p53-Mediated Downmodulation of CCR5 and HIV-1 Entry in Macrophages through MicroRNAs 103 and 107
title Interleukin-1β Triggers p53-Mediated Downmodulation of CCR5 and HIV-1 Entry in Macrophages through MicroRNAs 103 and 107
title_full Interleukin-1β Triggers p53-Mediated Downmodulation of CCR5 and HIV-1 Entry in Macrophages through MicroRNAs 103 and 107
title_fullStr Interleukin-1β Triggers p53-Mediated Downmodulation of CCR5 and HIV-1 Entry in Macrophages through MicroRNAs 103 and 107
title_full_unstemmed Interleukin-1β Triggers p53-Mediated Downmodulation of CCR5 and HIV-1 Entry in Macrophages through MicroRNAs 103 and 107
title_short Interleukin-1β Triggers p53-Mediated Downmodulation of CCR5 and HIV-1 Entry in Macrophages through MicroRNAs 103 and 107
title_sort interleukin-1β triggers p53-mediated downmodulation of ccr5 and hiv-1 entry in macrophages through micrornas 103 and 107
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527731/
https://www.ncbi.nlm.nih.gov/pubmed/32994328
http://dx.doi.org/10.1128/mBio.02314-20
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