Viral dosing of influenza A infection reveals involvement of RIPK3 and FADD, but not MLKL

RIPK3 was reported to play an important role in the protection against influenza A virus (IAV) in vivo. Here we show that the requirement of RIPK3 for protection against IAV infection in vivo is only apparent within a limited dose range of IAV challenge. We found that this protective outcome is inde...

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Autores principales: Oltean, Teodora, Van San, Emily, Divert, Tatyana, Vanden Berghe, Tom, Saelens, Xavier, Maelfait, Jonathan, Takahashi, Nozomi, Vandenabeele, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113499/
https://www.ncbi.nlm.nih.gov/pubmed/33976111
http://dx.doi.org/10.1038/s41419-021-03746-0
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author Oltean, Teodora
Van San, Emily
Divert, Tatyana
Vanden Berghe, Tom
Saelens, Xavier
Maelfait, Jonathan
Takahashi, Nozomi
Vandenabeele, Peter
author_facet Oltean, Teodora
Van San, Emily
Divert, Tatyana
Vanden Berghe, Tom
Saelens, Xavier
Maelfait, Jonathan
Takahashi, Nozomi
Vandenabeele, Peter
author_sort Oltean, Teodora
collection PubMed
description RIPK3 was reported to play an important role in the protection against influenza A virus (IAV) in vivo. Here we show that the requirement of RIPK3 for protection against IAV infection in vivo is only apparent within a limited dose range of IAV challenge. We found that this protective outcome is independent from RIPK3 kinase activity and from MLKL. This shows that platform function of RIPK3 rather than its kinase activity is required for protection, suggesting that a RIPK3 function independent of necroptosis is implicated. In line with this finding, we show that FADD-dependent apoptosis has a crucial additional effect in protection against IAV infection. Altogether, we show that RIPK3 contributes to protection against IAV in a narrow challenge dose range by a mechanism that is independent of its kinase activity and its capacity to induce necroptosis.
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spelling pubmed-81134992021-05-12 Viral dosing of influenza A infection reveals involvement of RIPK3 and FADD, but not MLKL Oltean, Teodora Van San, Emily Divert, Tatyana Vanden Berghe, Tom Saelens, Xavier Maelfait, Jonathan Takahashi, Nozomi Vandenabeele, Peter Cell Death Dis Article RIPK3 was reported to play an important role in the protection against influenza A virus (IAV) in vivo. Here we show that the requirement of RIPK3 for protection against IAV infection in vivo is only apparent within a limited dose range of IAV challenge. We found that this protective outcome is independent from RIPK3 kinase activity and from MLKL. This shows that platform function of RIPK3 rather than its kinase activity is required for protection, suggesting that a RIPK3 function independent of necroptosis is implicated. In line with this finding, we show that FADD-dependent apoptosis has a crucial additional effect in protection against IAV infection. Altogether, we show that RIPK3 contributes to protection against IAV in a narrow challenge dose range by a mechanism that is independent of its kinase activity and its capacity to induce necroptosis. Nature Publishing Group UK 2021-05-11 /pmc/articles/PMC8113499/ /pubmed/33976111 http://dx.doi.org/10.1038/s41419-021-03746-0 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Oltean, Teodora
Van San, Emily
Divert, Tatyana
Vanden Berghe, Tom
Saelens, Xavier
Maelfait, Jonathan
Takahashi, Nozomi
Vandenabeele, Peter
Viral dosing of influenza A infection reveals involvement of RIPK3 and FADD, but not MLKL
title Viral dosing of influenza A infection reveals involvement of RIPK3 and FADD, but not MLKL
title_full Viral dosing of influenza A infection reveals involvement of RIPK3 and FADD, but not MLKL
title_fullStr Viral dosing of influenza A infection reveals involvement of RIPK3 and FADD, but not MLKL
title_full_unstemmed Viral dosing of influenza A infection reveals involvement of RIPK3 and FADD, but not MLKL
title_short Viral dosing of influenza A infection reveals involvement of RIPK3 and FADD, but not MLKL
title_sort viral dosing of influenza a infection reveals involvement of ripk3 and fadd, but not mlkl
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113499/
https://www.ncbi.nlm.nih.gov/pubmed/33976111
http://dx.doi.org/10.1038/s41419-021-03746-0
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