Role of CCR3 in respiratory syncytial virus infection of airway epithelial cells

Vincent Wellemans; Hassan Ait Benhassou; Eloise Fuselier; Fabienne Bellesort; Sandra Dury; François Lebargy; Valérian Dormoy; Caroline Fichel; Richard Le Naour; Abdelilah S Gounni; Bouchaib Lamkhioued

doi:10.1016/j.isci.2021.103433

Role of CCR3 in respiratory syncytial virus infection of airway epithelial cells

iScience. 2021 Nov 14;24(12):103433. doi: 10.1016/j.isci.2021.103433. eCollection 2021 Dec 17.

Authors

Affiliations

¹ CHU Sainte-Justine, Montréal, Québec, Canada.
² Laboratoire d'Immunologie et de Biotechnologie, EA7509-IRMAIC, Pôle-Santé, Université de Reims Champagne-Ardenne, Reims, France.
³ Service des Maladies Respiratoires et Allergiques. Hôpital Maison Blanche, CHU de Reims, Reims, France.
⁴ Inserm UMR-S 1250, Pathologies Pulmonaires et Plasticité Cellulaire (P3Cell). Université de Reims Champagne-Ardenne, Reims, France.
⁵ Department of Immunology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Canada.

Abstract

Respiratory syncytial virus (RSV) infection is the principal cause of severe lower respiratory tract disease and accounts for a significant risk for developing asthma later in life. Clinical studies have shown an increase in airway responsiveness and a concomitant Th₂ response in the lungs of RSV-infected patients. These indications suggest that RSV may modulate aspects of the immune response to promote virus replication. Here, we show that CCR3 facilitates RSV infection of airway epithelial cells, an effect that was inhibited by eotaxin-1/CCL11 or upon CCR3 gene silencing. Mechanistically, cellular entry of RSV is mediated by binding of the viral G protein to CCR3 and selective chemotaxis of Th₂ cells and eosinophils. In vivo, mice lacking CCR3 display a significant reduction in RSV infection, airway inflammation, and mucus production. Overall, RSV G protein-CCR3 interaction may participate in pulmonary infection and inflammation by enhancing eosinophils' recruitment and less potent antiviral Th₂ cells.

Keywords: Cell biology; Immunology; Virology.