Differential effects of Usutu and West Nile viruses on neuroinflammation, immune cell recruitment and blood–brain barrier integrity

Usutu (USUV) and West Nile (WNV) viruses are two closely related Flavivirus belonging to Japanese encephalitis virus serogroup. Evidence of increased circulation of these two arboviruses now exist in Europe. Neurological disorders are reported in humans mainly for WNV, despite the fact that the inte...

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Main Authors: Orianne Constant, Ghizlane Maarifi, Jonathan Barthelemy, Marie-France Martin, Bachirou Tinto, Giovanni Savini, Philippe Van de Perre, Sébastien Nisole, Yannick Simonin, Sara Salinas
Format: Article
Language:English
Published: Taylor & Francis Group 2023-12-01
Series:Emerging Microbes and Infections
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Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2022.2156815
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author Orianne Constant
Ghizlane Maarifi
Jonathan Barthelemy
Marie-France Martin
Bachirou Tinto
Giovanni Savini
Philippe Van de Perre
Sébastien Nisole
Yannick Simonin
Sara Salinas
author_facet Orianne Constant
Ghizlane Maarifi
Jonathan Barthelemy
Marie-France Martin
Bachirou Tinto
Giovanni Savini
Philippe Van de Perre
Sébastien Nisole
Yannick Simonin
Sara Salinas
author_sort Orianne Constant
collection DOAJ
description Usutu (USUV) and West Nile (WNV) viruses are two closely related Flavivirus belonging to Japanese encephalitis virus serogroup. Evidence of increased circulation of these two arboviruses now exist in Europe. Neurological disorders are reported in humans mainly for WNV, despite the fact that the interaction and effects of viral infections on the neurovasculature are poorly described, notably for USUV. Using a human in vitro blood–brain barrier (BBB) and a mouse model, this study characterizes and compares the cerebral endothelial cell permissiveness, innate immunity and inflammatory responses and immune cell recruitment during infection by USUV and WNV. Both viruses are able to infect and cross the human BBB but with different consequences. We observed that WNV infects BBB cells resulting in significant endothelium impairment, potent neuroinflammation and immune cell recruitment, in agreement with previous studies. USUV, despite being able to infect BBB cells with higher replication rate than WNV, does not strongly affect endothelium integrity. Importantly, USUV also induces neuroinflammation, immune cell recruitment such as T lymphocytes, monocytes and dendritic cells (DCs) and was able to infect dendritic cells (DCs) more efficiently compared to WNV, with greater propensity for BBB recruitment. DCs may have differential roles for neuroinvasion of the two related viruses.
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spelling doaj-art-464f8757a2bd4da985bb9661e610a80f2025-08-20T01:49:09ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512023-12-0112110.1080/22221751.2022.2156815Differential effects of Usutu and West Nile viruses on neuroinflammation, immune cell recruitment and blood–brain barrier integrityOrianne Constant0Ghizlane Maarifi1Jonathan Barthelemy2Marie-France Martin3Bachirou Tinto4Giovanni Savini5Philippe Van de Perre6Sébastien Nisole7Yannick Simonin8Sara Salinas9Pathogenesis and Control of Chronic and Emerging Infections, INSERM, University of Montpellier, Etablissement Français du Sang, Montpellier, FranceCNRS, Institut de Recherche en Infectiologie de Montpellier, Université de Montpellier, Montpellier, FrancePathogenesis and Control of Chronic and Emerging Infections, INSERM, University of Montpellier, Etablissement Français du Sang, Montpellier, FranceCNRS, Institut de Recherche en Infectiologie de Montpellier, Université de Montpellier, Montpellier, FrancePathogenesis and Control of Chronic and Emerging Infections, INSERM, University of Montpellier, Etablissement Français du Sang, Montpellier, FranceIstituto Zooprofilattico Sperimentale dell'Abruzzo e del Molise (IZS-Teramo), Teramo, ItalyPathogenesis and Control of Chronic and Emerging Infections, INSERM, University of Montpellier, Etablissement Français du Sang, Montpellier, FranceCNRS, Institut de Recherche en Infectiologie de Montpellier, Université de Montpellier, Montpellier, FrancePathogenesis and Control of Chronic and Emerging Infections, INSERM, University of Montpellier, Etablissement Français du Sang, Montpellier, FrancePathogenesis and Control of Chronic and Emerging Infections, INSERM, University of Montpellier, Etablissement Français du Sang, Montpellier, FranceUsutu (USUV) and West Nile (WNV) viruses are two closely related Flavivirus belonging to Japanese encephalitis virus serogroup. Evidence of increased circulation of these two arboviruses now exist in Europe. Neurological disorders are reported in humans mainly for WNV, despite the fact that the interaction and effects of viral infections on the neurovasculature are poorly described, notably for USUV. Using a human in vitro blood–brain barrier (BBB) and a mouse model, this study characterizes and compares the cerebral endothelial cell permissiveness, innate immunity and inflammatory responses and immune cell recruitment during infection by USUV and WNV. Both viruses are able to infect and cross the human BBB but with different consequences. We observed that WNV infects BBB cells resulting in significant endothelium impairment, potent neuroinflammation and immune cell recruitment, in agreement with previous studies. USUV, despite being able to infect BBB cells with higher replication rate than WNV, does not strongly affect endothelium integrity. Importantly, USUV also induces neuroinflammation, immune cell recruitment such as T lymphocytes, monocytes and dendritic cells (DCs) and was able to infect dendritic cells (DCs) more efficiently compared to WNV, with greater propensity for BBB recruitment. DCs may have differential roles for neuroinvasion of the two related viruses.https://www.tandfonline.com/doi/10.1080/22221751.2022.2156815Usutu virusWest-Nile virusblood-brain barrierinnate immunityneuro-inflammationleukocytes
spellingShingle Orianne Constant
Ghizlane Maarifi
Jonathan Barthelemy
Marie-France Martin
Bachirou Tinto
Giovanni Savini
Philippe Van de Perre
Sébastien Nisole
Yannick Simonin
Sara Salinas
Differential effects of Usutu and West Nile viruses on neuroinflammation, immune cell recruitment and blood–brain barrier integrity
Emerging Microbes and Infections
Usutu virus
West-Nile virus
blood-brain barrier
innate immunity
neuro-inflammation
leukocytes
title Differential effects of Usutu and West Nile viruses on neuroinflammation, immune cell recruitment and blood–brain barrier integrity
title_full Differential effects of Usutu and West Nile viruses on neuroinflammation, immune cell recruitment and blood–brain barrier integrity
title_fullStr Differential effects of Usutu and West Nile viruses on neuroinflammation, immune cell recruitment and blood–brain barrier integrity
title_full_unstemmed Differential effects of Usutu and West Nile viruses on neuroinflammation, immune cell recruitment and blood–brain barrier integrity
title_short Differential effects of Usutu and West Nile viruses on neuroinflammation, immune cell recruitment and blood–brain barrier integrity
title_sort differential effects of usutu and west nile viruses on neuroinflammation immune cell recruitment and blood brain barrier integrity
topic Usutu virus
West-Nile virus
blood-brain barrier
innate immunity
neuro-inflammation
leukocytes
url https://www.tandfonline.com/doi/10.1080/22221751.2022.2156815
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