Antibody Neutralization of HIV-1 Crossing the Blood-Brain Barrier

ABSTRACT HIV-1 can cross the blood-brain barrier (BBB) to penetrate the brain and infect target cells, causing neurocognitive disorders as a result of neuroinflammation and brain damage. Here, we examined whether antibodies targeting the HIV-1 envelope glycoproteins interfere with the transcytosis o...

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Autores principales:	Valérie Lorin, Anne Danckaert, Françoise Porrot, Olivier Schwartz, Philippe V. Afonso, Hugo Mouquet
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	antibodies blood brain barrier HIV-1 neutralization transcytosis Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/9f247b0ebedf4ff9954a82cb5fc1720f
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spelling	oai:doaj.org-article:9f247b0ebedf4ff9954a82cb5fc1720f2021-11-15T16:19:09ZAntibody Neutralization of HIV-1 Crossing the Blood-Brain Barrier10.1128/mBio.02424-202150-7511https://doaj.org/article/9f247b0ebedf4ff9954a82cb5fc1720f2020-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02424-20https://doaj.org/toc/2150-7511ABSTRACT HIV-1 can cross the blood-brain barrier (BBB) to penetrate the brain and infect target cells, causing neurocognitive disorders as a result of neuroinflammation and brain damage. Here, we examined whether antibodies targeting the HIV-1 envelope glycoproteins interfere with the transcytosis of virions across the human BBB endothelium. We found that although the viral envelope spike gp160 is required for optimal endothelial cell endocytosis, no anti-gp160 antibodies blocked the BBB transcytosis of HIV-1 in vitro. Instead, both free viruses and those in complex with antibodies transited across endothelial cells in the BBB model, as observed by confocal microscopy. HIV-1 infectious capacity was considerably altered by the transcytosis process but still detectable, even in the presence of nonneutralizing antibodies. Only virions bound by neutralizing antibodies lacked posttranscytosis infectivity. Overall, our data support the role of neutralizing antibodies in protecting susceptible brain cells from HIV-1 infection despite their inability to inhibit viral BBB endocytic transport. IMPORTANCE HIV-1 can cross the blood-brain barrier (BBB) to penetrate the brain and infect target cells, causing neurocognitive disorders as a result of neuroinflammation and brain damage. The HIV-1 envelope spike gp160 is partially required for viral transcytosis across the BBB endothelium. But do antibodies developing in infected individuals and targeting the HIV-1 gp160 glycoproteins block HIV-1 transcytosis through the BBB? We addressed this issue and discovered that anti-gp160 antibodies do not block HIV-1 transport; instead, free viruses and those in complex with antibodies can transit across BBB endothelial cells. Importantly, we found that only neutralizing antibodies could inhibit posttranscytosis viral infectivity, highlighting their ability to protect susceptible brain cells from HIV-1 infection.Valérie LorinAnne DanckaertFrançoise PorrotOlivier SchwartzPhilippe V. AfonsoHugo MouquetAmerican Society for Microbiologyarticleantibodiesblood brain barrierHIV-1neutralizationtranscytosisMicrobiologyQR1-502ENmBio, Vol 11, Iss 5 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	antibodies blood brain barrier HIV-1 neutralization transcytosis Microbiology QR1-502
spellingShingle	antibodies blood brain barrier HIV-1 neutralization transcytosis Microbiology QR1-502 Valérie Lorin Anne Danckaert Françoise Porrot Olivier Schwartz Philippe V. Afonso Hugo Mouquet Antibody Neutralization of HIV-1 Crossing the Blood-Brain Barrier
description	ABSTRACT HIV-1 can cross the blood-brain barrier (BBB) to penetrate the brain and infect target cells, causing neurocognitive disorders as a result of neuroinflammation and brain damage. Here, we examined whether antibodies targeting the HIV-1 envelope glycoproteins interfere with the transcytosis of virions across the human BBB endothelium. We found that although the viral envelope spike gp160 is required for optimal endothelial cell endocytosis, no anti-gp160 antibodies blocked the BBB transcytosis of HIV-1 in vitro. Instead, both free viruses and those in complex with antibodies transited across endothelial cells in the BBB model, as observed by confocal microscopy. HIV-1 infectious capacity was considerably altered by the transcytosis process but still detectable, even in the presence of nonneutralizing antibodies. Only virions bound by neutralizing antibodies lacked posttranscytosis infectivity. Overall, our data support the role of neutralizing antibodies in protecting susceptible brain cells from HIV-1 infection despite their inability to inhibit viral BBB endocytic transport. IMPORTANCE HIV-1 can cross the blood-brain barrier (BBB) to penetrate the brain and infect target cells, causing neurocognitive disorders as a result of neuroinflammation and brain damage. The HIV-1 envelope spike gp160 is partially required for viral transcytosis across the BBB endothelium. But do antibodies developing in infected individuals and targeting the HIV-1 gp160 glycoproteins block HIV-1 transcytosis through the BBB? We addressed this issue and discovered that anti-gp160 antibodies do not block HIV-1 transport; instead, free viruses and those in complex with antibodies can transit across BBB endothelial cells. Importantly, we found that only neutralizing antibodies could inhibit posttranscytosis viral infectivity, highlighting their ability to protect susceptible brain cells from HIV-1 infection.
format	article
author	Valérie Lorin Anne Danckaert Françoise Porrot Olivier Schwartz Philippe V. Afonso Hugo Mouquet
author_facet	Valérie Lorin Anne Danckaert Françoise Porrot Olivier Schwartz Philippe V. Afonso Hugo Mouquet
author_sort	Valérie Lorin
title	Antibody Neutralization of HIV-1 Crossing the Blood-Brain Barrier
title_short	Antibody Neutralization of HIV-1 Crossing the Blood-Brain Barrier
title_full	Antibody Neutralization of HIV-1 Crossing the Blood-Brain Barrier
title_fullStr	Antibody Neutralization of HIV-1 Crossing the Blood-Brain Barrier
title_full_unstemmed	Antibody Neutralization of HIV-1 Crossing the Blood-Brain Barrier
title_sort	antibody neutralization of hiv-1 crossing the blood-brain barrier
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/9f247b0ebedf4ff9954a82cb5fc1720f
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Antibody Neutralization of HIV-1 Crossing the Blood-Brain Barrier

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