Protein phosphatase 1 abrogates IRF7-mediated type I IFN response in antiviral immunity
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim..
Interferon (IFN) regulatory factor 7 (IRF7) plays a key role in the production of IFN-α in response to viral infection, and phosphorylation at IRF7 C-terminal serine sites is prelude to its function. However, phosphatases that negatively regulate IRF7 phosphorylation and activity have not been reported. In this study, we have identified a conserved protein phosphatase 1 (PP1)-binding motif in human and mouse IRF7 proteins, and shown that PP1 physically interacts with IRF7. Exogenous expression of PP1 subunits (PP1α, β, or γ) ablates IKKε-stimulated IRF7 phosphorylation and dramatically attenuates IRF7 transcriptional activity. Inhibition of PP1 activity significantly increases IRF7 phosphorylation and IRF7-mediated IFN-α production in response to Newcastle disease virus (NDV) infection or Toll-like receptor 7 (TLR7) challenge, leading to impaired viral replication. In addition, IFN treatment, TLR challenges and viral infection induce PP1 expression. Our findings disclose for the first time a pivotal role for PP1 in impeding IRF7-mediated IFN-α production in host immune responses.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2016 |
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| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:46 |
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| Enthalten in: |
European journal of immunology - 46(2016), 10 vom: 20. Okt., Seite 2409-2419 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Ling [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 28.06.2017 Date Revised 13.11.2018 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/eji.201646491 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM262912252 |
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| 245 | 1 | 0 | |a Protein phosphatase 1 abrogates IRF7-mediated type I IFN response in antiviral immunity |
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| 500 | |a Date Revised 13.11.2018 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. | ||
| 520 | |a Interferon (IFN) regulatory factor 7 (IRF7) plays a key role in the production of IFN-α in response to viral infection, and phosphorylation at IRF7 C-terminal serine sites is prelude to its function. However, phosphatases that negatively regulate IRF7 phosphorylation and activity have not been reported. In this study, we have identified a conserved protein phosphatase 1 (PP1)-binding motif in human and mouse IRF7 proteins, and shown that PP1 physically interacts with IRF7. Exogenous expression of PP1 subunits (PP1α, β, or γ) ablates IKKε-stimulated IRF7 phosphorylation and dramatically attenuates IRF7 transcriptional activity. Inhibition of PP1 activity significantly increases IRF7 phosphorylation and IRF7-mediated IFN-α production in response to Newcastle disease virus (NDV) infection or Toll-like receptor 7 (TLR7) challenge, leading to impaired viral replication. In addition, IFN treatment, TLR challenges and viral infection induce PP1 expression. Our findings disclose for the first time a pivotal role for PP1 in impeding IRF7-mediated IFN-α production in host immune responses | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a IRF7 | |
| 650 | 4 | |a PP1 | |
| 650 | 4 | |a TLR7 | |
| 650 | 4 | |a Type I IFN | |
| 650 | 7 | |a IRF7 protein, human |2 NLM | |
| 650 | 7 | |a Interferon Regulatory Factor-7 |2 NLM | |
| 650 | 7 | |a Interferon-alpha |2 NLM | |
| 650 | 7 | |a RNA, Small Interfering |2 NLM | |
| 650 | 7 | |a Protein Phosphatase 1 |2 NLM | |
| 650 | 7 | |a EC 3.1.3.16 |2 NLM | |
| 700 | 1 | |a Zhao, Juan |e verfasserin |4 aut | |
| 700 | 1 | |a Ren, Junping |e verfasserin |4 aut | |
| 700 | 1 | |a Hall, Kenton H |e verfasserin |4 aut | |
| 700 | 1 | |a Moorman, Jonathan P |e verfasserin |4 aut | |
| 700 | 1 | |a Yao, Zhi Q |e verfasserin |4 aut | |
| 700 | 1 | |a Ning, Shunbin |e verfasserin |4 aut | |
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