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

doi:10.1016/j.isci.2020.101256

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 journal › Article › peer-review

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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 language	English
Article number	101256
Journal	iScience
Volume	23
Issue number	7
DOIs	https://doi.org/10.1016/j.isci.2020.101256
State	Published - Jul 24 2020

Keywords

Cell Biology
Immunology
Virology

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10.1016/j.isci.2020.101256

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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), Article 101256. https://doi.org/10.1016/j.isci.2020.101256

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title = "Interleukin-22 Inhibits Respiratory Syncytial Virus Production by Blocking Virus-Mediated Subversion of Cellular Autophagy",

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.",

keywords = "Cell Biology, Immunology, Virology",

author = "Sudipta Das and {St. Croix}, Claudette and Misty Good and Jie Chen and Jinming Zhao and Sanmei Hu and Mark Ross and Myerburg, {Michael M.} and Pilewski, {Joseph M.} and John Williams and Wenzel, {Sally E.} and Kolls, {Jay K.} and Anuradha Ray and Prabir Ray",

note = "Funding Information: The authors thank Morgan Jessup for assistance with confocal microscopy, Drs. Stokes Peebles and Martin Moore for sharing the RSV strains, Dr. J.E. Durbin for providing NY3.2 STAT1 −/− cells, and Dr. Sreejata Raychaudhuri for performing pilot immunoblotting experiments. This work was supported by the National Institutes of Health grants AI100012 , HL122307 , and HL114453 (to P.R.) and HL113956 , AI106684 , and AI048927 (to A. R.). Publisher Copyright: {\textcopyright} 2020 The Authors",

year = "2020",

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doi = "10.1016/j.isci.2020.101256",

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AU - St. Croix, Claudette

AU - Good, Misty

AU - Chen, Jie

AU - Zhao, Jinming

AU - Hu, Sanmei

AU - Ross, Mark

AU - Myerburg, Michael M.

AU - Pilewski, Joseph M.

AU - Williams, John

AU - Wenzel, Sally E.

AU - Kolls, Jay K.

AU - Ray, Anuradha

AU - Ray, Prabir

N1 - Funding Information: The authors thank Morgan Jessup for assistance with confocal microscopy, Drs. Stokes Peebles and Martin Moore for sharing the RSV strains, Dr. J.E. Durbin for providing NY3.2 STAT1 −/− cells, and Dr. Sreejata Raychaudhuri for performing pilot immunoblotting experiments. This work was supported by the National Institutes of Health grants AI100012 , HL122307 , and HL114453 (to P.R.) and HL113956 , AI106684 , and AI048927 (to A. R.). Publisher Copyright: © 2020 The Authors

PY - 2020/7/24

Y1 - 2020/7/24

N2 - 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.

AB - 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.

KW - Cell Biology

KW - Immunology

KW - Virology

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ER -

Interleukin-22 Inhibits Respiratory Syncytial Virus Production by Blocking Virus-Mediated Subversion of Cellular Autophagy

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