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Necroptosis restricts influenza A virus as a stand-alone cell death mechanism
Influenza A virus (IAV) activates ZBP1-initiated RIPK3-dependent parallel pathways of necroptosis and apoptosis in infected cells. Although mice deficient in both pathways fail to control IAV and succumb to lethal respiratory infection, RIPK3-mediated apoptosis by itself can limit IAV, without need...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596817/ https://www.ncbi.nlm.nih.gov/pubmed/32797196 http://dx.doi.org/10.1084/jem.20191259 |
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author | Shubina, Maria Tummers, Bart Boyd, David F. Zhang, Ting Yin, Chaoran Gautam, Avishekh Guo, Xi-zhi J. Rodriguez, Diego A. Kaiser, William J. Vogel, Peter Green, Douglas R. Thomas, Paul G. Balachandran, Siddharth |
author_facet | Shubina, Maria Tummers, Bart Boyd, David F. Zhang, Ting Yin, Chaoran Gautam, Avishekh Guo, Xi-zhi J. Rodriguez, Diego A. Kaiser, William J. Vogel, Peter Green, Douglas R. Thomas, Paul G. Balachandran, Siddharth |
author_sort | Shubina, Maria |
collection | PubMed |
description | Influenza A virus (IAV) activates ZBP1-initiated RIPK3-dependent parallel pathways of necroptosis and apoptosis in infected cells. Although mice deficient in both pathways fail to control IAV and succumb to lethal respiratory infection, RIPK3-mediated apoptosis by itself can limit IAV, without need for necroptosis. However, whether necroptosis, conventionally considered a fail-safe cell death mechanism to apoptosis, can restrict IAV—or indeed any virus—in the absence of apoptosis is not known. Here, we use mice selectively deficient in IAV-activated apoptosis to show that necroptosis drives robust antiviral immune responses and promotes effective virus clearance from infected lungs when apoptosis is absent. We also demonstrate that apoptosis and necroptosis are mutually exclusive fates in IAV-infected cells. Thus, necroptosis is an independent, “stand-alone” cell death mechanism that fully compensates for the absence of apoptosis in antiviral host defense. |
format | Online Article Text |
id | pubmed-7596817 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-75968172021-05-02 Necroptosis restricts influenza A virus as a stand-alone cell death mechanism Shubina, Maria Tummers, Bart Boyd, David F. Zhang, Ting Yin, Chaoran Gautam, Avishekh Guo, Xi-zhi J. Rodriguez, Diego A. Kaiser, William J. Vogel, Peter Green, Douglas R. Thomas, Paul G. Balachandran, Siddharth J Exp Med Brief Definitive Report Influenza A virus (IAV) activates ZBP1-initiated RIPK3-dependent parallel pathways of necroptosis and apoptosis in infected cells. Although mice deficient in both pathways fail to control IAV and succumb to lethal respiratory infection, RIPK3-mediated apoptosis by itself can limit IAV, without need for necroptosis. However, whether necroptosis, conventionally considered a fail-safe cell death mechanism to apoptosis, can restrict IAV—or indeed any virus—in the absence of apoptosis is not known. Here, we use mice selectively deficient in IAV-activated apoptosis to show that necroptosis drives robust antiviral immune responses and promotes effective virus clearance from infected lungs when apoptosis is absent. We also demonstrate that apoptosis and necroptosis are mutually exclusive fates in IAV-infected cells. Thus, necroptosis is an independent, “stand-alone” cell death mechanism that fully compensates for the absence of apoptosis in antiviral host defense. Rockefeller University Press 2020-08-14 /pmc/articles/PMC7596817/ /pubmed/32797196 http://dx.doi.org/10.1084/jem.20191259 Text en © 2020 Shubina 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 | Brief Definitive Report Shubina, Maria Tummers, Bart Boyd, David F. Zhang, Ting Yin, Chaoran Gautam, Avishekh Guo, Xi-zhi J. Rodriguez, Diego A. Kaiser, William J. Vogel, Peter Green, Douglas R. Thomas, Paul G. Balachandran, Siddharth Necroptosis restricts influenza A virus as a stand-alone cell death mechanism |
title | Necroptosis restricts influenza A virus as a stand-alone cell death mechanism |
title_full | Necroptosis restricts influenza A virus as a stand-alone cell death mechanism |
title_fullStr | Necroptosis restricts influenza A virus as a stand-alone cell death mechanism |
title_full_unstemmed | Necroptosis restricts influenza A virus as a stand-alone cell death mechanism |
title_short | Necroptosis restricts influenza A virus as a stand-alone cell death mechanism |
title_sort | necroptosis restricts influenza a virus as a stand-alone cell death mechanism |
topic | Brief Definitive Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596817/ https://www.ncbi.nlm.nih.gov/pubmed/32797196 http://dx.doi.org/10.1084/jem.20191259 |
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