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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2021
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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. |
format | Online Article Text |
id | pubmed-8092320 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
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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