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.