摘要：SummaryRespiratory syncytial virus (RSV) infection can cause severe bronchiolitis in infants requiring hospitalization, whereas the elderly and immunocompromised are prone to RSV-induced pneumonia. RSV primarily infects lung epithelial cells. Given that no vaccine against RSV is currently available, we tested the ability of the epithelial-barrier protective cytokine interleukin-22 (IL-22) to control RSV production. When used in a therapeutic modality, IL-22 efficiently blunted RSV production from infected human airway and alveolar epithelial cells and IL-22 administration drastically reduced virus titer in the lungs of infected newborn mice. RSV infection resulted in increased expression of LC3B, a key component of the cellular autophagic machinery, and knockdown of LC3B ablated virus production. RSV subverted LC3B with evidence of co-localization and caused a significant reduction in autophagic flux, both reversed by IL-22 treatment. Our findings inform a previously unrecognized anti-viral effect of IL-22 that can be harnessed to prevent RSV-induced severe respiratory disease.Graphical AbstractDisplay OmittedHighlights•RSV infection of lung epithelial cells subverts the cellular autophagic machinery•RSV infection inhibits autophagic flux in infected cells•IL-22 inhibits RSV production from human lung epithelial cells and in neonatal mice•IL-22 blocks RSV-LC3B co-localization and restores cellular autophagic fluxImmunology; Virology; Cell Biology
