Protein Phosphatase 1 Abrogates IRF7-Mediated Type I IFN Response In Antiviral Immunity

Ling Wang; Juan Zhao; Junping Ren; Kenton H. Hall; Jonathan P. Moorman; Zhi Q. Yao; Shunbin Ning

doi:10.1002/eji.201646491

Protein Phosphatase 1 Abrogates IRF7-Mediated Type I IFN Response In Antiviral Immunity

Ling Wang
, Juan Zhao
, Junping Ren
, Kenton H. Hall
, Jonathan P. Moorman
, Zhi Q. Yao
, Shunbin Ning

Department of Internal Medicine

East Tennessee State University

Research output: Contribution to journal › Article › peer-review

Abstract

<p> Interferon (IFN) regulatory factor 7 (IRF7) plays a key role in the production of IFN&hyphen;α in response to viral infection, and phosphorylation at IRF7 C&hyphen;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)&hyphen;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&hyphen;stimulated IRF7 phosphorylation and dramatically attenuates IRF7 transcriptional activity. Inhibition of PP1 activity significantly increases IRF7 phosphorylation and IRF7&hyphen;mediated IFN&hyphen;α production in response to Newcastle disease virus (NDV) infection or Toll&hyphen;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&hyphen;mediated IFN&hyphen;α production in host immune responses.</p>

Original language	American English
Journal	European Journal of Immunology
Volume	46
DOIs	https://doi.org/10.1002/eji.201646491
State	Published - May 1 2016

Keywords

IRF7-Mediated Type I IFN
antiviral immunity
protein phosphatase 1

Disciplines

Internal Medicine

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title = "Protein Phosphatase 1 Abrogates IRF7-Mediated Type I IFN Response In Antiviral Immunity",

abstract = " Interferon (IFN) regulatory factor 7 (IRF7) plays a key role in the production of IFN\&hyphen;\α in response to viral infection, and phosphorylation at IRF7 C\&hyphen;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)\&hyphen;binding motif in human and mouse IRF7 proteins, and shown that PP1 physically interacts with IRF7. Exogenous expression of PP1 subunits (PP1\α, \β, or \γ) ablates IKK\ε\&hyphen;stimulated IRF7 phosphorylation and dramatically attenuates IRF7 transcriptional activity. Inhibition of PP1 activity significantly increases IRF7 phosphorylation and IRF7\&hyphen;mediated IFN\&hyphen;\α production in response to Newcastle disease virus (NDV) infection or Toll\&hyphen;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\&hyphen;mediated IFN\&hyphen;\α production in host immune responses.",

keywords = "IRF7-Mediated Type I IFN, antiviral immunity, protein phosphatase 1",

author = "Ling Wang and Juan Zhao and Junping Ren and Hall, \{Kenton H.\} and Moorman, \{Jonathan P.\} and Yao, \{Zhi Q.\} and Shunbin Ning",

year = "2016",

month = may,

day = "1",

doi = "10.1002/eji.201646491",

language = "American English",

volume = "46",

journal = "European Journal of Immunology",

}

TY - JOUR

T1 - Protein Phosphatase 1 Abrogates IRF7-Mediated Type I IFN Response In Antiviral Immunity

AU - Wang, Ling

AU - Zhao, Juan

AU - Ren, Junping

AU - Hall, Kenton H.

AU - Moorman, Jonathan P.

AU - Yao, Zhi Q.

AU - Ning, Shunbin

PY - 2016/5/1

Y1 - 2016/5/1

N2 - Interferon (IFN) regulatory factor 7 (IRF7) plays a key role in the production of IFN&hyphen;α in response to viral infection, and phosphorylation at IRF7 C&hyphen;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)&hyphen;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&hyphen;stimulated IRF7 phosphorylation and dramatically attenuates IRF7 transcriptional activity. Inhibition of PP1 activity significantly increases IRF7 phosphorylation and IRF7&hyphen;mediated IFN&hyphen;α production in response to Newcastle disease virus (NDV) infection or Toll&hyphen;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&hyphen;mediated IFN&hyphen;α production in host immune responses.

AB - Interferon (IFN) regulatory factor 7 (IRF7) plays a key role in the production of IFN&hyphen;α in response to viral infection, and phosphorylation at IRF7 C&hyphen;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)&hyphen;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&hyphen;stimulated IRF7 phosphorylation and dramatically attenuates IRF7 transcriptional activity. Inhibition of PP1 activity significantly increases IRF7 phosphorylation and IRF7&hyphen;mediated IFN&hyphen;α production in response to Newcastle disease virus (NDV) infection or Toll&hyphen;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&hyphen;mediated IFN&hyphen;α production in host immune responses.

KW - IRF7-Mediated Type I IFN

KW - antiviral immunity

KW - protein phosphatase 1

UR - https://dc.etsu.edu/etsu-works/6519

U2 - 10.1002/eji.201646491

DO - 10.1002/eji.201646491

M3 - Article

VL - 46

JO - European Journal of Immunology

JF - European Journal of Immunology

ER -

Protein Phosphatase 1 Abrogates IRF7-Mediated Type I IFN Response In Antiviral Immunity

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