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-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.
authors.affiliation: Center of Excellence for Inflammation, Infectious Diseases and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.|Department of Internal Medicine, East Tennessee State University, Quillen College of Medicine, Johnson City, TN, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine, East Tennessee State University, Quillen College of Medicine, Johnson City, TN, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Center of Excellence for Inflammation, Infectious Diseases and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.|Department of Internal Medicine, East Tennessee State University, Quillen College of Medicine, Johnson City, TN, USA.
authors.forename: Junping
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Internal Medicine, East Tennessee State University, Quillen College of Medicine, Johnson City, TN, USA.
authors.forename: Kenton H
authors.initials: KH
authors.lastname: Hall
authors.affiliation: Center of Excellence for Inflammation, Infectious Diseases and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.|Department of Internal Medicine, East Tennessee State University, Quillen College of Medicine, Johnson City, TN, USA.|Hepatitis (HCV/HIV) Program, James H Quillen VA Medical Center, Johnson City, TN, USA.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Moorman
authors.affiliation: Center of Excellence for Inflammation, Infectious Diseases and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.|Department of Internal Medicine, East Tennessee State University, Quillen College of Medicine, Johnson City, TN, USA.|Hepatitis (HCV/HIV) Program, James H Quillen VA Medical Center, Johnson City, TN, USA.
authors.forename: Zhi Q
authors.initials: ZQ
authors.lastname: Yao
authors.affiliation: Center of Excellence for Inflammation, Infectious Diseases and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA. nings1@etsu.edu.|Department of Internal Medicine, East Tennessee State University, Quillen College of Medicine, Johnson City, TN, USA. nings1@etsu.edu.
authors.forename: Shunbin
authors.initials: S
authors.lastname: Ning
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics; D000818:Animals; D057809:HEK293 Cells; D006801:Humans; D007109:Immunity / Q000235:genetics; D050839:Interferon Regulatory Factor-7 / Q000378:metabolism; D016898:Interferon-alpha / Q000378:metabolism; D051379:Mice; D009521:Newcastle Disease / Q000276:immunology*; D009522:Newcastle disease virus / Q000276:immunology*; D010766:Phosphorylation / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D054645:Protein Phosphatase 1 / Q000235:genetics / Q000378:metabolism*; D000067996:RAW 264.7 Cells; D034741:RNA, Small Interfering / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics; D019076:Transgenes / Q000235:genetics
chemical_list: C494234:IRF7 protein, human; D050839:Interferon Regulatory Factor-7; D016898:Interferon-alpha; D034741:RNA, Small Interfering; D054645:Protein Phosphatase 1
keywords: IRF7; PP1; TLR7; Type I IFN