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...
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American Society for Microbiology
2020
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oai:doaj.org-article:a806d0852bba4648addb7368645ffcc72021-11-15T15:56:43ZZika Virus Infection Promotes Local Inflammation, Cell Adhesion Molecule Upregulation, and Leukocyte Recruitment at the Blood-Brain Barrier10.1128/mBio.01183-202150-7511https://doaj.org/article/a806d0852bba4648addb7368645ffcc72020-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01183-20https://doaj.org/toc/2150-7511ABSTRACT 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.Marion CléCaroline DesmetzJonathan BarthelemyMarie-France MartinOrianne ConstantGhizlane MaarifiVincent FoulongneKarine BolloréYaël GlassonFrédéric De BockMarine BlaquiereLucie DehouckNelly PirotEdouard TuaillonSébastien NisoleFatiha NajioullahPhilippe Van de PerreAndré CabiéNicola MarchiFabien GosseletYannick SimoninSara SalinasAmerican Society for MicrobiologyarticleZika virusblood-brain barriercell adhesion moleculesleukocyte recruitmentMicrobiologyQR1-502ENmBio, Vol 11, Iss 4 (2020) |
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| collection |
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| topic |
Zika virus blood-brain barrier cell adhesion molecules leukocyte recruitment Microbiology QR1-502 |
| spellingShingle |
Zika virus blood-brain barrier cell adhesion molecules leukocyte recruitment Microbiology QR1-502 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 |
| 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. |
| format |
article |
| 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 |
| title |
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_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_sort |
zika virus infection promotes local inflammation, cell adhesion molecule upregulation, and leukocyte recruitment at the blood-brain barrier |
| publisher |
American Society for Microbiology |
| publishDate |
2020 |
| url |
https://doaj.org/article/a806d0852bba4648addb7368645ffcc7 |
| work_keys_str_mv |
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