Interleukin-22 Inhibits Respiratory Syncytial Virus Production by Blocking Virus-Mediated Subversion of Cellular Autophagy
Sudipta Das,
Claudette St. Croix,
Misty Good,
Jie Chen,
Jinming Zhao,
Sanmei Hu,
Mark Ross,
Michael M. Myerburg,
Joseph M. Pilewski,
John Williams,
Sally E. Wenzel,
Jay K. Kolls,
Anuradha Ray,
Prabir Ray
Affiliations
Sudipta Das
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, 3459 Fifth Avenue, MUH 628 NW, Pittsburgh, PA 15213, USA
Claudette St. Croix
Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Misty Good
Division of Newborn Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA
Jie Chen
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, 3459 Fifth Avenue, MUH 628 NW, Pittsburgh, PA 15213, USA
Jinming Zhao
Department of Environmental Medicine and Occupational Health, Graduate School of Public Health, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Sanmei Hu
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, 3459 Fifth Avenue, MUH 628 NW, Pittsburgh, PA 15213, USA
Mark Ross
Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Michael M. Myerburg
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, 3459 Fifth Avenue, MUH 628 NW, Pittsburgh, PA 15213, USA
Joseph M. Pilewski
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, 3459 Fifth Avenue, MUH 628 NW, Pittsburgh, PA 15213, USA
John Williams
Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Sally E. Wenzel
Department of Environmental Medicine and Occupational Health, Graduate School of Public Health, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Jay K. Kolls
Department of Medicine, Center for Translational Research in Infection and Inflammation, Tulane School of Medicine, New Orleans, LA, USA
Anuradha Ray
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, 3459 Fifth Avenue, MUH 628 NW, Pittsburgh, PA 15213, USA; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Prabir Ray
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, 3459 Fifth Avenue, MUH 628 NW, Pittsburgh, PA 15213, USA; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Corresponding author
Summary: Respiratory 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.
