title: Suppression of type I interferon production by porcine epidemic diarrhea virus and degradation of CREB-binding protein by nsp1.
abstract: Type I interferons (IFN-α/β) are the major components of the innate immune response of hosts, and in turn many viruses have evolved to modulate the host response during infection. We found that the IFN-β production was significantly suppressed during PEDV infection in cells. To identify viral IFN antagonists and to study their suppressive function, viral coding sequences for the entire structural and nonstructural proteins were cloned and expressed. Of 16 PEDV nonstructural proteins (nsps), nsp1, nsp3, nsp7, nsp14, nsp15 and nsp16 were found to inhibit the IFN-β and IRF3 promoter activities. The sole accessory protein ORF3, structure protein envelope (E), membrane (M), and nucleocapsid (N) protein were also shown to inhibit such activities. PEDV nsp1 did not interfere the IRF3 phosphorylation and nuclear translocation but interrupted the enhanceosome assembly of IRF3 and CREB-binding protein (CBP) by degrading CBP. A further study showed that the CBP degradation by nsp1 was proteasome-dependent. Our data demonstrate that PEDV modulates the host innate immune responses by degrading CBP and suppressing ISGs expression.
authors.affiliation: Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana 61802, IL, USA.
authors.forename: Qingzhan
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana 61802, IL, USA.
authors.forename: Kaichuang
authors.initials: K
authors.lastname: Shi
authors.affiliation: Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana 61802, IL, USA. Electronic address: dyoo@illinois.edu.
authors.forename: Dongwan
authors.initials: D
authors.lastname: Yoo
mesh_terms: D000818:Animals; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism / Q000821:virology; D018352:Coronavirus Infections / Q000235:genetics / Q000378:metabolism / Q000662:veterinary* / Q000821:virology; D015536:Down-Regulation; D054884:Host-Pathogen Interactions; D016899:Interferon-beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D053485:Porcine epidemic diarrhea virus / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D059748:Proteolysis; D013552:Swine; D013553:Swine Diseases / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D017361:Viral Nonstructural Proteins; D016899:Interferon-beta; D050882:CREB-Binding Protein
keywords: CBP; CREB-binding protein; Coronavirus; Innate immune signaling; Interferon regulation; Nsp1; Porcine epidemic diarrhea virus