Defective viral genomes arising in vivo provide critical danger signals for the triggering of lung antiviral immunity.
The innate immune response to viruses is initiated when specialized cellular sensors recognize viral danger signals. Here we show that truncated forms of viral genomes that accumulate in infected cells potently trigger the sustained activation of the transcription factors IRF3 and NF-κB and the prod...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-10-01
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| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC3814336?pdf=render |
| _version_ | 1818981482471882752 |
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| author | Karla Tapia Won-Keun Kim Yan Sun Xiomara Mercado-López Emily Dunay Megan Wise Michael Adu Carolina B López |
| author_facet | Karla Tapia Won-Keun Kim Yan Sun Xiomara Mercado-López Emily Dunay Megan Wise Michael Adu Carolina B López |
| author_sort | Karla Tapia |
| collection | DOAJ |
| description | The innate immune response to viruses is initiated when specialized cellular sensors recognize viral danger signals. Here we show that truncated forms of viral genomes that accumulate in infected cells potently trigger the sustained activation of the transcription factors IRF3 and NF-κB and the production type I IFNs through a mechanism independent of IFN signaling. We demonstrate that these defective viral genomes (DVGs) are generated naturally during respiratory infections in vivo even in mice lacking the type I IFN receptor, and their appearance coincides with the production of cytokines during infections with Sendai virus (SeV) or influenza virus. Remarkably, the hallmark antiviral cytokine IFNβ is only expressed in lung epithelial cells containing DVGs, while cells within the lung that contain standard viral genomes alone do not express this cytokine. Together, our data indicate that DVGs generated during viral replication are a primary source of danger signals for the initiation of the host immune response to infection. |
| first_indexed | 2024-12-20T17:32:01Z |
| format | Article |
| id | doaj.art-e829f6399df14ecfa75532b2aa639874 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-20T17:32:01Z |
| publishDate | 2013-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-e829f6399df14ecfa75532b2aa6398742022-12-21T19:31:21ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742013-10-01910e100370310.1371/journal.ppat.1003703Defective viral genomes arising in vivo provide critical danger signals for the triggering of lung antiviral immunity.Karla TapiaWon-Keun KimYan SunXiomara Mercado-LópezEmily DunayMegan WiseMichael AduCarolina B LópezThe innate immune response to viruses is initiated when specialized cellular sensors recognize viral danger signals. Here we show that truncated forms of viral genomes that accumulate in infected cells potently trigger the sustained activation of the transcription factors IRF3 and NF-κB and the production type I IFNs through a mechanism independent of IFN signaling. We demonstrate that these defective viral genomes (DVGs) are generated naturally during respiratory infections in vivo even in mice lacking the type I IFN receptor, and their appearance coincides with the production of cytokines during infections with Sendai virus (SeV) or influenza virus. Remarkably, the hallmark antiviral cytokine IFNβ is only expressed in lung epithelial cells containing DVGs, while cells within the lung that contain standard viral genomes alone do not express this cytokine. Together, our data indicate that DVGs generated during viral replication are a primary source of danger signals for the initiation of the host immune response to infection.http://europepmc.org/articles/PMC3814336?pdf=render |
| spellingShingle | Karla Tapia Won-Keun Kim Yan Sun Xiomara Mercado-López Emily Dunay Megan Wise Michael Adu Carolina B López Defective viral genomes arising in vivo provide critical danger signals for the triggering of lung antiviral immunity. PLoS Pathogens |
| title | Defective viral genomes arising in vivo provide critical danger signals for the triggering of lung antiviral immunity. |
| title_full | Defective viral genomes arising in vivo provide critical danger signals for the triggering of lung antiviral immunity. |
| title_fullStr | Defective viral genomes arising in vivo provide critical danger signals for the triggering of lung antiviral immunity. |
| title_full_unstemmed | Defective viral genomes arising in vivo provide critical danger signals for the triggering of lung antiviral immunity. |
| title_short | Defective viral genomes arising in vivo provide critical danger signals for the triggering of lung antiviral immunity. |
| title_sort | defective viral genomes arising in vivo provide critical danger signals for the triggering of lung antiviral immunity |
| url | http://europepmc.org/articles/PMC3814336?pdf=render |
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