Zika Virus Infection Promotes Local Inflammation, Cell Adhesion Molecule Upregulation, and Leukocyte Recruitment at the Blood-Brain Barrier
ABSTRACT The blood-brain barrier (BBB) largely prevents toxins and pathogens from accessing the brain. Some viruses have the ability to cross this barrier and replicate in the central nervous system (CNS). Zika virus (ZIKV) was responsible in 2015 to 2016 for a major epidemic in South America and wa...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2020-08-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.01183-20 |
| _version_ | 1818406304653246464 |
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| author | Marion Clé Caroline Desmetz Jonathan Barthelemy Marie-France Martin Orianne Constant Ghizlane Maarifi Vincent Foulongne Karine Bolloré Yaël Glasson Frédéric De Bock Marine Blaquiere Lucie Dehouck Nelly Pirot Edouard Tuaillon Sébastien Nisole Fatiha Najioullah Philippe Van de Perre André Cabié Nicola Marchi Fabien Gosselet Yannick Simonin Sara Salinas |
| author_facet | Marion Clé Caroline Desmetz Jonathan Barthelemy Marie-France Martin Orianne Constant Ghizlane Maarifi Vincent Foulongne Karine Bolloré Yaël Glasson Frédéric De Bock Marine Blaquiere Lucie Dehouck Nelly Pirot Edouard Tuaillon Sébastien Nisole Fatiha Najioullah Philippe Van de Perre André Cabié Nicola Marchi Fabien Gosselet Yannick Simonin Sara Salinas |
| author_sort | Marion Clé |
| collection | DOAJ |
| description | ABSTRACT The blood-brain barrier (BBB) largely prevents toxins and pathogens from accessing the brain. Some viruses have the ability to cross this barrier and replicate in the central nervous system (CNS). Zika virus (ZIKV) was responsible in 2015 to 2016 for a major epidemic in South America and was associated in some cases with neurological impairments. Here, we characterized some of the mechanisms behind its neuroinvasion using an innovative in vitro human BBB model. ZIKV efficiently replicated, was released on the BBB parenchyma side, and triggered subtle modulation of BBB integrity as well as an upregulation of inflammatory and cell adhesion molecules (CAMs), which in turn favored leukocyte recruitment. Finally, we showed that ZIKV-infected mouse models displayed similar CAM upregulation and that soluble CAMs were increased in plasma samples from ZIKV-infected patients. Our observations suggest a complex interplay between ZIKV and the BBB, which may trigger local inflammation, leukocyte recruitment, and possible cerebral vasculature impairment. IMPORTANCE Zika virus (ZIKV) can be associated with neurological impairment in children and adults. To reach the central nervous system, viruses have to cross the blood-brain barrier (BBB), a multicellular system allowing a tight separation between the bloodstream and the brain. Here, we show that ZIKV infects cells of the BBB and triggers a subtle change in its permeability. Moreover, ZIKV infection leads to the production of inflammatory molecules known to modulate BBB integrity and participate in immune cell attraction. The virus also led to the upregulation of cellular adhesion molecules (CAMs), which in turn favored immune cell binding to the BBB and potentially increased infiltration into the brain. These results were also observed in a mouse model of ZIKV infection. Furthermore, plasma samples from ZIKV-infected patients displayed an increase in CAMs, suggesting that this mechanism could be involved in neuroinflammation triggered by ZIKV. |
| first_indexed | 2024-12-14T09:09:49Z |
| format | Article |
| id | doaj.art-a806d0852bba4648addb7368645ffcc7 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-14T09:09:49Z |
| publishDate | 2020-08-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-a806d0852bba4648addb7368645ffcc72022-12-21T23:08:35ZengAmerican Society for MicrobiologymBio2150-75112020-08-0111410.1128/mBio.01183-20Zika Virus Infection Promotes Local Inflammation, Cell Adhesion Molecule Upregulation, and Leukocyte Recruitment at the Blood-Brain BarrierMarion Clé0Caroline Desmetz1Jonathan Barthelemy2Marie-France Martin3Orianne Constant4Ghizlane Maarifi5Vincent Foulongne6Karine Bolloré7Yaël Glasson8Frédéric De Bock9Marine Blaquiere10Lucie Dehouck11Nelly Pirot12Edouard Tuaillon13Sébastien Nisole14Fatiha Najioullah15Philippe Van de Perre16André Cabié17Nicola Marchi18Fabien Gosselet19Yannick Simonin20Sara Salinas21Pathogenesis and Control of Chronic Infections, INSERM, Université de Montpellier, Etablissement Français du Sang, Montpellier, FranceBioCommunication en CardioMétabolique, Université de Montpellier, Montpellier, FrancePathogenesis and Control of Chronic Infections, INSERM, Université de Montpellier, Etablissement Français du Sang, Montpellier, FranceInstitut de Recherche en Infectiologie de Montpellier, CNRS, Université de Montpellier, Montpellier, FrancePathogenesis and Control of Chronic Infections, INSERM, Université de Montpellier, Etablissement Français du Sang, Montpellier, FranceInstitut de Recherche en Infectiologie de Montpellier, CNRS, Université de Montpellier, Montpellier, FrancePathogenesis and Control of Chronic Infections, INSERM, Université de Montpellier, Etablissement Français du Sang, Montpellier, FrancePathogenesis and Control of Chronic Infections, INSERM, Université de Montpellier, Etablissement Français du Sang, Montpellier, FranceRéseau d'Histologie Expérimentale de Montpellier, BioCampus, CNRS, INSERM, Université de Montpellier, Montpellier, FranceCerebrovascular Mechanisms of Brain Disorders, Institute of Functional Genomics, CNRS, INSERM, University of Montpellier, Montpellier, FranceCerebrovascular Mechanisms of Brain Disorders, Institute of Functional Genomics, CNRS, INSERM, University of Montpellier, Montpellier, FranceLaboratoire de la Barrière Hémato-Encéphalique, Université d’Artois, Lens, FranceRéseau d'Histologie Expérimentale de Montpellier, BioCampus, CNRS, INSERM, Université de Montpellier, Montpellier, FrancePathogenesis and Control of Chronic Infections, INSERM, Université de Montpellier, Etablissement Français du Sang, Montpellier, FranceInstitut de Recherche en Infectiologie de Montpellier, CNRS, Université de Montpellier, Montpellier, FranceEA7524, Tropical and Infectious Disease Service, University of the Antilles, INSERM, Centre Hospitalier Universitaire de Martinique, Hôpital Pierre-Zobda-Quitman, Martinique, FrancePathogenesis and Control of Chronic Infections, INSERM, Université de Montpellier, Etablissement Français du Sang, Montpellier, FranceEA7524, Tropical and Infectious Disease Service, University of the Antilles, INSERM, Centre Hospitalier Universitaire de Martinique, Hôpital Pierre-Zobda-Quitman, Martinique, FranceCerebrovascular Mechanisms of Brain Disorders, Institute of Functional Genomics, CNRS, INSERM, University of Montpellier, Montpellier, FranceLaboratoire de la Barrière Hémato-Encéphalique, Université d’Artois, Lens, FrancePathogenesis and Control of Chronic Infections, INSERM, Université de Montpellier, Etablissement Français du Sang, Montpellier, FrancePathogenesis and Control of Chronic Infections, INSERM, Université de Montpellier, Etablissement Français du Sang, Montpellier, FranceABSTRACT The blood-brain barrier (BBB) largely prevents toxins and pathogens from accessing the brain. Some viruses have the ability to cross this barrier and replicate in the central nervous system (CNS). Zika virus (ZIKV) was responsible in 2015 to 2016 for a major epidemic in South America and was associated in some cases with neurological impairments. Here, we characterized some of the mechanisms behind its neuroinvasion using an innovative in vitro human BBB model. ZIKV efficiently replicated, was released on the BBB parenchyma side, and triggered subtle modulation of BBB integrity as well as an upregulation of inflammatory and cell adhesion molecules (CAMs), which in turn favored leukocyte recruitment. Finally, we showed that ZIKV-infected mouse models displayed similar CAM upregulation and that soluble CAMs were increased in plasma samples from ZIKV-infected patients. Our observations suggest a complex interplay between ZIKV and the BBB, which may trigger local inflammation, leukocyte recruitment, and possible cerebral vasculature impairment. IMPORTANCE Zika virus (ZIKV) can be associated with neurological impairment in children and adults. To reach the central nervous system, viruses have to cross the blood-brain barrier (BBB), a multicellular system allowing a tight separation between the bloodstream and the brain. Here, we show that ZIKV infects cells of the BBB and triggers a subtle change in its permeability. Moreover, ZIKV infection leads to the production of inflammatory molecules known to modulate BBB integrity and participate in immune cell attraction. The virus also led to the upregulation of cellular adhesion molecules (CAMs), which in turn favored immune cell binding to the BBB and potentially increased infiltration into the brain. These results were also observed in a mouse model of ZIKV infection. Furthermore, plasma samples from ZIKV-infected patients displayed an increase in CAMs, suggesting that this mechanism could be involved in neuroinflammation triggered by ZIKV.https://journals.asm.org/doi/10.1128/mBio.01183-20Zika virusblood-brain barriercell adhesion moleculesleukocyte recruitment |
| spellingShingle | Marion Clé Caroline Desmetz Jonathan Barthelemy Marie-France Martin Orianne Constant Ghizlane Maarifi Vincent Foulongne Karine Bolloré Yaël Glasson Frédéric De Bock Marine Blaquiere Lucie Dehouck Nelly Pirot Edouard Tuaillon Sébastien Nisole Fatiha Najioullah Philippe Van de Perre André Cabié Nicola Marchi Fabien Gosselet Yannick Simonin Sara Salinas Zika Virus Infection Promotes Local Inflammation, Cell Adhesion Molecule Upregulation, and Leukocyte Recruitment at the Blood-Brain Barrier mBio Zika virus blood-brain barrier cell adhesion molecules leukocyte recruitment |
| title | Zika Virus Infection Promotes Local Inflammation, Cell Adhesion Molecule Upregulation, and Leukocyte Recruitment at the Blood-Brain Barrier |
| title_full | Zika Virus Infection Promotes Local Inflammation, Cell Adhesion Molecule Upregulation, and Leukocyte Recruitment at the Blood-Brain Barrier |
| title_fullStr | Zika Virus Infection Promotes Local Inflammation, Cell Adhesion Molecule Upregulation, and Leukocyte Recruitment at the Blood-Brain Barrier |
| title_full_unstemmed | Zika Virus Infection Promotes Local Inflammation, Cell Adhesion Molecule Upregulation, and Leukocyte Recruitment at the Blood-Brain Barrier |
| title_short | Zika Virus Infection Promotes Local Inflammation, Cell Adhesion Molecule Upregulation, and Leukocyte Recruitment at the Blood-Brain Barrier |
| title_sort | zika virus infection promotes local inflammation cell adhesion molecule upregulation and leukocyte recruitment at the blood brain barrier |
| topic | Zika virus blood-brain barrier cell adhesion molecules leukocyte recruitment |
| url | https://journals.asm.org/doi/10.1128/mBio.01183-20 |
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