Rift Valley fever virus is able to cross the human blood-brain barrier in vitro by direct infection with no deleterious effects

Quellec Jordan, Piro-Megy Camille, Cannac Marion, Nisole Sébastien, Marty Florent H., Gosselet Fabien, Shimizu Fumitaka, Kanda Takashi, Cetre-Sossah Catherine, Salinas Sara. 2024. Rift Valley fever virus is able to cross the human blood-brain barrier in vitro by direct infection with no deleterious effects. Journal of Virology, 98 (10), 22 p.

https://doi.org/10.1128/jvi.01267-24

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Liste HCERES des revues (en SHS) : oui

Thème(s) HCERES des revues (en SHS) : Psychologie-éthologie-ergonomie

Résumé : Rift Valley fever (RVF) is a zoonotic arboviral disease that causes recurrent epidemics in Africa that may trigger fatal neurological disorders. However, the mechanisms of neuroinvasion by which the RVF virus (RVFV) reaches the human central nervous system (CNS) remain poorly characterized. In particular, it is not clear how RVFV is able to cross the human blood–brain barrier (hBBB), which is a neurovascular endothelium that protects the brain by regulating brain and blood exchanges. To explore these mechanisms, we used an in vitro hBBB model to mimic in vivo hBBB selectiveness and apicobasal polarity. Our results highlight the ability of RVFV to cross the hBBB by direct infection in a non-structural protein S (NSs)-independent but strain-dependent manner, leading to astrocyte and pericyte infections. Interestingly, RVFV infection did not induce hBBB disruption and was associated with progressive elimination of infected cells with no impairment of the tight junction protein scaffold and barrier function. Our work also shows that NSs, a well described RVFV virulence factor, limited the establishment of the hBBB-induced innate immune response and subsequent lymphocyte recruitment. These results provide in vitro confirmation of the ability of RVFV to reach human CNS by direct infection of the hBBB without altering its barrier function, and provide new directions to explore human RVFV neurovirulence and neuroinvasion mechanisms.

Mots-clés Agrovoc : Virus de la fièvre de la vallée du Rift, fièvre de la Vallée du Rift, réponse immunitaire, transmission des maladies, zoonose, épidémiologie, maladie de l'homme, virulence, infection

Mots-clés libres : Rift Valley fever virus, Blood brain barrier, Neuroinvasion, Immune response, Endothelium integrity

Classification Agris : S50 - Santé humaine
L73 - Maladies des animaux

Champ stratégique Cirad : CTS 4 (2019-) - Santé des plantes, des animaux et des écosystèmes

Agences de financement hors UE : Montpellier Université d'Excellence, Agence Nationale de la Recherche

Projets sur financement : (FRA) Caractéristiques cliniques et mécanismes moléculaires de la neuroinflammation et des dommages neurovasculaires induits par les arbovirus

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