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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number101256
JournaliScience
Volume23
Issue number7
DOIs
StatePublished - Jul 24 2020

Keywords

  • Cell Biology
  • Immunology
  • Virology

Fingerprint Dive into the research topics of 'Interleukin-22 Inhibits Respiratory Syncytial Virus Production by Blocking Virus-Mediated Subversion of Cellular Autophagy'. Together they form a unique fingerprint.

  • Cite this

    Das, S., St. Croix, C., Good, M., Chen, J., Zhao, J., Hu, S., Ross, M., Myerburg, M. M., Pilewski, J. M., Williams, J., Wenzel, S. E., Kolls, J. K., Ray, A., & Ray, P. (2020). Interleukin-22 Inhibits Respiratory Syncytial Virus Production by Blocking Virus-Mediated Subversion of Cellular Autophagy. iScience, 23(7), [101256]. https://doi.org/10.1016/j.isci.2020.101256