Optineurin negatively regulates the induction of IFNbeta in response to RNA virus infection.
The innate immune response provides a critical defense against microbial infections, including viruses. These are recognised by pattern recognition receptors including Toll-like receptors (TLRs) and RIG-I like helicases (RLHs). Detection of virus triggers signalling cascades that induce transcriptio...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-02-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1000778&type=printable |
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| _version_ | 1849736244051836928 |
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| author | Jamel Mankouri Rennos Fragkoudis Kathryn H Richards Laura F Wetherill Mark Harris Alain Kohl Richard M Elliott Andrew Macdonald |
| author_facet | Jamel Mankouri Rennos Fragkoudis Kathryn H Richards Laura F Wetherill Mark Harris Alain Kohl Richard M Elliott Andrew Macdonald |
| author_sort | Jamel Mankouri |
| collection | DOAJ |
| description | The innate immune response provides a critical defense against microbial infections, including viruses. These are recognised by pattern recognition receptors including Toll-like receptors (TLRs) and RIG-I like helicases (RLHs). Detection of virus triggers signalling cascades that induce transcription of type I interferons including IFNbeta, which are pivotal for the initiation of an anti-viral state. Despite the essential role of IFNbeta in the anti-viral response, there is an incomplete understanding of the negative regulation of IFNbeta induction. Here we provide evidence that expression of the Nemo-related protein, optineurin (NRP/FIP2), has a role in the inhibition of virus-triggered IFNbeta induction. Over-expression of optineurin inhibited Sendai-virus (SeV) and dsRNA triggered induction of IFNbeta, whereas depletion of optineurin with siRNA promoted virus-induced IFNbeta production and decreased RNA virus replication. Immunoprecipitation and immunofluorescence studies identified optineurin in a protein complex containing the antiviral protein kinase TBK1 and the ubiquitin ligase TRAF3. Furthermore, mutagenesis studies determined that binding of ubiquitin was essential for both the correct sub-cellular localisation and the inhibitory function of optineurin. This work identifies optineurin as a critical regulator of antiviral signalling and potential target for future antiviral therapy. |
| format | Article |
| id | doaj-art-8b1cdff4e5f94af59bc041f47ac7542d |
| institution | DOAJ |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2010-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-8b1cdff4e5f94af59bc041f47ac7542d2025-08-20T03:07:20ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742010-02-0162e100077810.1371/journal.ppat.1000778Optineurin negatively regulates the induction of IFNbeta in response to RNA virus infection.Jamel MankouriRennos FragkoudisKathryn H RichardsLaura F WetherillMark HarrisAlain KohlRichard M ElliottAndrew MacdonaldThe innate immune response provides a critical defense against microbial infections, including viruses. These are recognised by pattern recognition receptors including Toll-like receptors (TLRs) and RIG-I like helicases (RLHs). Detection of virus triggers signalling cascades that induce transcription of type I interferons including IFNbeta, which are pivotal for the initiation of an anti-viral state. Despite the essential role of IFNbeta in the anti-viral response, there is an incomplete understanding of the negative regulation of IFNbeta induction. Here we provide evidence that expression of the Nemo-related protein, optineurin (NRP/FIP2), has a role in the inhibition of virus-triggered IFNbeta induction. Over-expression of optineurin inhibited Sendai-virus (SeV) and dsRNA triggered induction of IFNbeta, whereas depletion of optineurin with siRNA promoted virus-induced IFNbeta production and decreased RNA virus replication. Immunoprecipitation and immunofluorescence studies identified optineurin in a protein complex containing the antiviral protein kinase TBK1 and the ubiquitin ligase TRAF3. Furthermore, mutagenesis studies determined that binding of ubiquitin was essential for both the correct sub-cellular localisation and the inhibitory function of optineurin. This work identifies optineurin as a critical regulator of antiviral signalling and potential target for future antiviral therapy.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1000778&type=printable |
| spellingShingle | Jamel Mankouri Rennos Fragkoudis Kathryn H Richards Laura F Wetherill Mark Harris Alain Kohl Richard M Elliott Andrew Macdonald Optineurin negatively regulates the induction of IFNbeta in response to RNA virus infection. PLoS Pathogens |
| title | Optineurin negatively regulates the induction of IFNbeta in response to RNA virus infection. |
| title_full | Optineurin negatively regulates the induction of IFNbeta in response to RNA virus infection. |
| title_fullStr | Optineurin negatively regulates the induction of IFNbeta in response to RNA virus infection. |
| title_full_unstemmed | Optineurin negatively regulates the induction of IFNbeta in response to RNA virus infection. |
| title_short | Optineurin negatively regulates the induction of IFNbeta in response to RNA virus infection. |
| title_sort | optineurin negatively regulates the induction of ifnbeta in response to rna virus infection |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1000778&type=printable |
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