Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2020
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
_version_ 1783602193007378432
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
work_keys_str_mv AT shubinamaria necroptosisrestrictsinfluenzaavirusasastandalonecelldeathmechanism
AT tummersbart necroptosisrestrictsinfluenzaavirusasastandalonecelldeathmechanism
AT boyddavidf necroptosisrestrictsinfluenzaavirusasastandalonecelldeathmechanism
AT zhangting necroptosisrestrictsinfluenzaavirusasastandalonecelldeathmechanism
AT yinchaoran necroptosisrestrictsinfluenzaavirusasastandalonecelldeathmechanism
AT gautamavishekh necroptosisrestrictsinfluenzaavirusasastandalonecelldeathmechanism
AT guoxizhij necroptosisrestrictsinfluenzaavirusasastandalonecelldeathmechanism
AT rodriguezdiegoa necroptosisrestrictsinfluenzaavirusasastandalonecelldeathmechanism
AT kaiserwilliamj necroptosisrestrictsinfluenzaavirusasastandalonecelldeathmechanism
AT vogelpeter necroptosisrestrictsinfluenzaavirusasastandalonecelldeathmechanism
AT greendouglasr necroptosisrestrictsinfluenzaavirusasastandalonecelldeathmechanism
AT thomaspaulg necroptosisrestrictsinfluenzaavirusasastandalonecelldeathmechanism
AT balachandransiddharth necroptosisrestrictsinfluenzaavirusasastandalonecelldeathmechanism