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Defective viral genomes arising in vivo provide critical danger signals for the triggering of lung antiviral immunity.


ABSTRACT: 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-?B 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 IFN? 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.

SUBMITTER: Tapia K 

PROVIDER: S-EPMC3814336 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Defective viral genomes arising in vivo provide critical danger signals for the triggering of lung antiviral immunity.

Tapia Karla K   Kim Won-Keun WK   Sun Yan Y   Mercado-López Xiomara X   Dunay Emily E   Wise Megan M   Adu Michael M   López Carolina B CB  

PLoS pathogens 20131031 10


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  ...[more]

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