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Central Nervous System (CNS) Viral Seeding by Mature Monocytes and Potential Therapies To Reduce CNS Viral Reservoirs in the cART Era

The human immunodeficiency virus (HIV) enters the central nervous system (CNS) within a few days after primary infection, establishing viral reservoirs that persist even with combined antiretroviral therapy (cART). We show that monocytes from people living with HIV (PLWH) on suppressive cART harbori...

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Autores principales: León-Rivera, Rosiris, Veenstra, Mike, Donoso, Maribel, Tell, Elizabeth, Eugenin, Eliseo A., Morgello, Susan, Berman, Joan W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092320/
https://www.ncbi.nlm.nih.gov/pubmed/33727362
http://dx.doi.org/10.1128/mBio.03633-20
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author León-Rivera, Rosiris
Veenstra, Mike
Donoso, Maribel
Tell, Elizabeth
Eugenin, Eliseo A.
Morgello, Susan
Berman, Joan W.
author_facet León-Rivera, Rosiris
Veenstra, Mike
Donoso, Maribel
Tell, Elizabeth
Eugenin, Eliseo A.
Morgello, Susan
Berman, Joan W.
author_sort León-Rivera, Rosiris
collection PubMed
description The human immunodeficiency virus (HIV) enters the central nervous system (CNS) within a few days after primary infection, establishing viral reservoirs that persist even with combined antiretroviral therapy (cART). We show that monocytes from people living with HIV (PLWH) on suppressive cART harboring integrated HIV, viral mRNA, and/or viral proteins preferentially transmigrate across the blood-brain barrier (BBB) to CCL2 and are significantly enriched post-transmigration, and even more highly enriched posttransmigration than T cells with similar properties. Using HIV-infected ART-treated mature monocytes cultured in vitro, we recapitulate these findings and demonstrate that HIV(+) CD14(+) CD16(+) ART-treated monocytes also preferentially transmigrate. Cenicriviroc and anti-JAM-A and anti-ALCAM antibodies significantly and preferentially reduce/block transmigration of HIV(+) CD14(+) CD16(+) ART-treated monocytes. These findings highlight the importance of monocytes in CNS HIV reservoirs and suggest targets to eliminate their formation and reseeding.
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spelling pubmed-80923202021-05-04 Central Nervous System (CNS) Viral Seeding by Mature Monocytes and Potential Therapies To Reduce CNS Viral Reservoirs in the cART Era León-Rivera, Rosiris Veenstra, Mike Donoso, Maribel Tell, Elizabeth Eugenin, Eliseo A. Morgello, Susan Berman, Joan W. mBio Research Article The human immunodeficiency virus (HIV) enters the central nervous system (CNS) within a few days after primary infection, establishing viral reservoirs that persist even with combined antiretroviral therapy (cART). We show that monocytes from people living with HIV (PLWH) on suppressive cART harboring integrated HIV, viral mRNA, and/or viral proteins preferentially transmigrate across the blood-brain barrier (BBB) to CCL2 and are significantly enriched post-transmigration, and even more highly enriched posttransmigration than T cells with similar properties. Using HIV-infected ART-treated mature monocytes cultured in vitro, we recapitulate these findings and demonstrate that HIV(+) CD14(+) CD16(+) ART-treated monocytes also preferentially transmigrate. Cenicriviroc and anti-JAM-A and anti-ALCAM antibodies significantly and preferentially reduce/block transmigration of HIV(+) CD14(+) CD16(+) ART-treated monocytes. These findings highlight the importance of monocytes in CNS HIV reservoirs and suggest targets to eliminate their formation and reseeding. American Society for Microbiology 2021-03-16 /pmc/articles/PMC8092320/ /pubmed/33727362 http://dx.doi.org/10.1128/mBio.03633-20 Text en Copyright © 2021 León-Rivera 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
León-Rivera, Rosiris
Veenstra, Mike
Donoso, Maribel
Tell, Elizabeth
Eugenin, Eliseo A.
Morgello, Susan
Berman, Joan W.
Central Nervous System (CNS) Viral Seeding by Mature Monocytes and Potential Therapies To Reduce CNS Viral Reservoirs in the cART Era
title Central Nervous System (CNS) Viral Seeding by Mature Monocytes and Potential Therapies To Reduce CNS Viral Reservoirs in the cART Era
title_full Central Nervous System (CNS) Viral Seeding by Mature Monocytes and Potential Therapies To Reduce CNS Viral Reservoirs in the cART Era
title_fullStr Central Nervous System (CNS) Viral Seeding by Mature Monocytes and Potential Therapies To Reduce CNS Viral Reservoirs in the cART Era
title_full_unstemmed Central Nervous System (CNS) Viral Seeding by Mature Monocytes and Potential Therapies To Reduce CNS Viral Reservoirs in the cART Era
title_short Central Nervous System (CNS) Viral Seeding by Mature Monocytes and Potential Therapies To Reduce CNS Viral Reservoirs in the cART Era
title_sort central nervous system (cns) viral seeding by mature monocytes and potential therapies to reduce cns viral reservoirs in the cart era
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092320/
https://www.ncbi.nlm.nih.gov/pubmed/33727362
http://dx.doi.org/10.1128/mBio.03633-20
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