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ZBP1/DAI ubiquitination and sensing of influenza vRNPs activate programmed cell death

Innate sensing of influenza virus infection induces activation of programmed cell death pathways. We have recently identified Z-DNA–binding protein 1 (ZBP1) as an innate sensor of influenza A virus (IAV). ZBP1-mediated IAV sensing is critical for triggering programmed cell death in the infected lung...

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Autores principales: Kesavardhana, Sannula, Kuriakose, Teneema, Guy, Clifford S., Samir, Parimal, Malireddi, R.K. Subbarao, Mishra, Ashutosh, Kanneganti, Thirumala-Devi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5551577/
https://www.ncbi.nlm.nih.gov/pubmed/28634194
http://dx.doi.org/10.1084/jem.20170550
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author Kesavardhana, Sannula
Kuriakose, Teneema
Guy, Clifford S.
Samir, Parimal
Malireddi, R.K. Subbarao
Mishra, Ashutosh
Kanneganti, Thirumala-Devi
author_facet Kesavardhana, Sannula
Kuriakose, Teneema
Guy, Clifford S.
Samir, Parimal
Malireddi, R.K. Subbarao
Mishra, Ashutosh
Kanneganti, Thirumala-Devi
author_sort Kesavardhana, Sannula
collection PubMed
description Innate sensing of influenza virus infection induces activation of programmed cell death pathways. We have recently identified Z-DNA–binding protein 1 (ZBP1) as an innate sensor of influenza A virus (IAV). ZBP1-mediated IAV sensing is critical for triggering programmed cell death in the infected lungs. Surprisingly, little is known about the mechanisms regulating ZBP1 activation to induce programmed cell death. Here, we report that the sensing of IAV RNA by retinoic acid inducible gene I (RIG-I) initiates ZBP1-mediated cell death via the RIG-I–MAVS–IFN-β signaling axis. IAV infection induces ubiquitination of ZBP1, suggesting potential regulation of ZBP1 function through posttranslational modifications. We further demonstrate that ZBP1 senses viral ribonucleoprotein (vRNP) complexes of IAV to trigger cell death. These findings collectively indicate that ZBP1 activation requires RIG-I signaling, ubiquitination, and vRNP sensing to trigger activation of programmed cell death pathways during IAV infection. The mechanism of ZBP1 activation described here may have broader implications in the context of virus-induced cell death.
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spelling pubmed-55515772018-02-07 ZBP1/DAI ubiquitination and sensing of influenza vRNPs activate programmed cell death Kesavardhana, Sannula Kuriakose, Teneema Guy, Clifford S. Samir, Parimal Malireddi, R.K. Subbarao Mishra, Ashutosh Kanneganti, Thirumala-Devi J Exp Med Research Articles Innate sensing of influenza virus infection induces activation of programmed cell death pathways. We have recently identified Z-DNA–binding protein 1 (ZBP1) as an innate sensor of influenza A virus (IAV). ZBP1-mediated IAV sensing is critical for triggering programmed cell death in the infected lungs. Surprisingly, little is known about the mechanisms regulating ZBP1 activation to induce programmed cell death. Here, we report that the sensing of IAV RNA by retinoic acid inducible gene I (RIG-I) initiates ZBP1-mediated cell death via the RIG-I–MAVS–IFN-β signaling axis. IAV infection induces ubiquitination of ZBP1, suggesting potential regulation of ZBP1 function through posttranslational modifications. We further demonstrate that ZBP1 senses viral ribonucleoprotein (vRNP) complexes of IAV to trigger cell death. These findings collectively indicate that ZBP1 activation requires RIG-I signaling, ubiquitination, and vRNP sensing to trigger activation of programmed cell death pathways during IAV infection. The mechanism of ZBP1 activation described here may have broader implications in the context of virus-induced cell death. The Rockefeller University Press 2017-08-07 /pmc/articles/PMC5551577/ /pubmed/28634194 http://dx.doi.org/10.1084/jem.20170550 Text en © 2017 Kesavardhana et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Kesavardhana, Sannula
Kuriakose, Teneema
Guy, Clifford S.
Samir, Parimal
Malireddi, R.K. Subbarao
Mishra, Ashutosh
Kanneganti, Thirumala-Devi
ZBP1/DAI ubiquitination and sensing of influenza vRNPs activate programmed cell death
title ZBP1/DAI ubiquitination and sensing of influenza vRNPs activate programmed cell death
title_full ZBP1/DAI ubiquitination and sensing of influenza vRNPs activate programmed cell death
title_fullStr ZBP1/DAI ubiquitination and sensing of influenza vRNPs activate programmed cell death
title_full_unstemmed ZBP1/DAI ubiquitination and sensing of influenza vRNPs activate programmed cell death
title_short ZBP1/DAI ubiquitination and sensing of influenza vRNPs activate programmed cell death
title_sort zbp1/dai ubiquitination and sensing of influenza vrnps activate programmed cell death
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5551577/
https://www.ncbi.nlm.nih.gov/pubmed/28634194
http://dx.doi.org/10.1084/jem.20170550
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