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Replication defective viral genomes exploit a cellular pro-survival mechanism to establish paramyxovirus persistence
Replication defective viral genomes (DVGs) generated during virus replication are the primary triggers of antiviral immunity in many RNA virus infections. However, DVGs can also facilitate viral persistence. Why and how these two opposing functions of DVGs are achieved remain unknown. Here we report...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5630589/ https://www.ncbi.nlm.nih.gov/pubmed/28986577 http://dx.doi.org/10.1038/s41467-017-00909-6 |
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author | Xu, Jie Sun, Yan Li, Yize Ruthel, Gordon Weiss, Susan R. Raj, Arjun Beiting, Daniel López, Carolina B. |
author_facet | Xu, Jie Sun, Yan Li, Yize Ruthel, Gordon Weiss, Susan R. Raj, Arjun Beiting, Daniel López, Carolina B. |
author_sort | Xu, Jie |
collection | PubMed |
description | Replication defective viral genomes (DVGs) generated during virus replication are the primary triggers of antiviral immunity in many RNA virus infections. However, DVGs can also facilitate viral persistence. Why and how these two opposing functions of DVGs are achieved remain unknown. Here we report that during Sendai and respiratory syncytial virus infections DVGs selectively protect a subpopulation of cells from death, thereby promoting the establishment of persistent infections. We find that during Sendai virus infection this phenotype results from DVGs stimulating a mitochondrial antiviral-signaling (MAVS)-mediated TNF response that drives apoptosis of highly infected cells while extending the survival of cells enriched in DVGs. The pro-survival effect of TNF depends on the activity of the TNFR2/TRAF1 pathway that is regulated by MAVS signaling. These results identify TNF as a pivotal factor in determining cell fate during a viral infection and delineate a MAVS/TNFR2-mediated mechanism that drives the persistence of otherwise acute viruses. |
format | Online Article Text |
id | pubmed-5630589 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-56305892017-10-10 Replication defective viral genomes exploit a cellular pro-survival mechanism to establish paramyxovirus persistence Xu, Jie Sun, Yan Li, Yize Ruthel, Gordon Weiss, Susan R. Raj, Arjun Beiting, Daniel López, Carolina B. Nat Commun Article Replication defective viral genomes (DVGs) generated during virus replication are the primary triggers of antiviral immunity in many RNA virus infections. However, DVGs can also facilitate viral persistence. Why and how these two opposing functions of DVGs are achieved remain unknown. Here we report that during Sendai and respiratory syncytial virus infections DVGs selectively protect a subpopulation of cells from death, thereby promoting the establishment of persistent infections. We find that during Sendai virus infection this phenotype results from DVGs stimulating a mitochondrial antiviral-signaling (MAVS)-mediated TNF response that drives apoptosis of highly infected cells while extending the survival of cells enriched in DVGs. The pro-survival effect of TNF depends on the activity of the TNFR2/TRAF1 pathway that is regulated by MAVS signaling. These results identify TNF as a pivotal factor in determining cell fate during a viral infection and delineate a MAVS/TNFR2-mediated mechanism that drives the persistence of otherwise acute viruses. Nature Publishing Group UK 2017-10-06 /pmc/articles/PMC5630589/ /pubmed/28986577 http://dx.doi.org/10.1038/s41467-017-00909-6 Text en © The Author(s) 2017 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/. |
spellingShingle | Article Xu, Jie Sun, Yan Li, Yize Ruthel, Gordon Weiss, Susan R. Raj, Arjun Beiting, Daniel López, Carolina B. Replication defective viral genomes exploit a cellular pro-survival mechanism to establish paramyxovirus persistence |
title | Replication defective viral genomes exploit a cellular pro-survival mechanism to establish paramyxovirus persistence |
title_full | Replication defective viral genomes exploit a cellular pro-survival mechanism to establish paramyxovirus persistence |
title_fullStr | Replication defective viral genomes exploit a cellular pro-survival mechanism to establish paramyxovirus persistence |
title_full_unstemmed | Replication defective viral genomes exploit a cellular pro-survival mechanism to establish paramyxovirus persistence |
title_short | Replication defective viral genomes exploit a cellular pro-survival mechanism to establish paramyxovirus persistence |
title_sort | replication defective viral genomes exploit a cellular pro-survival mechanism to establish paramyxovirus persistence |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5630589/ https://www.ncbi.nlm.nih.gov/pubmed/28986577 http://dx.doi.org/10.1038/s41467-017-00909-6 |
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