title: Interferon priming enables cells to partially overturn the SARS coronavirus-induced block in innate immune activation.
abstract: SARS coronavirus (SARS-CoV) is known to efficiently suppress the induction of antiviral type I interferons (IFN-alpha/beta) in non-lymphatic cells through inhibition of the transcription factor IRF-3. Plasmacytoid dendritic cells, in contrast, respond to infection with production of high levels of IFNs. Here, we show that pretreatment of non-lymphatic cells with small amounts of IFN-alpha (IFN priming) partially overturns the block in IFN induction imposed by SARS-CoV. IFN priming combined with SARS-CoV infection substantially induced genes for IFN induction, IFN signalling, antiviral effector proteins, ubiquitination and ISGylation, antigen presentation and other cytokines and chemokines, whereas each individual treatment had no major effect. Curiously, however, despite this typical IFN response, neither IRF-3 nor IRF-7 was transported to the nucleus as a sign of activation. Taken together, our results suggest that (i) IFN, as it is produced by plasmacytoid dendritic cells, could enable tissue cells to launch a host response to SARS-CoV, (ii) IRF-3 and IRF-7 may be active at subdetectable levels, and (iii) SARS-CoV does not activate IRF-7.
authors.affiliation: Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, D-79008 Freiburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kuri
authors.affiliation: Research Unit, Shanghai Public Health Clinical Center, and Key Laboratory of Medical Molecular Virology, Fudan University, Shanghai, PR China.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, D-79008 Freiburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Habjan
authors.affiliation: School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642, USA.
authors.forename: Luis
authors.initials: L
authors.lastname: Martínez-Sobrido
authors.affiliation: Department of Microbiology, Department of Medicine (Division of Infectious Diseases) and Global Health and Emerging Pathogens Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
authors.affiliation: Research Unit, Shanghai Public Health Clinical Center, and Key Laboratory of Medical Molecular Virology, Fudan University, Shanghai, PR China.
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, D-79008 Freiburg, Germany.
authors.forename: Friedemann
authors.initials: F
authors.lastname: Weber
mesh_terms: D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D050839:Interferon Regulatory Factor-7 / Q000378:metabolism; D016898:Interferon-alpha / Q000276:immunology*; D021381:Protein Transport; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology*
chemical_list: D016207:Cytokines; D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D016898:Interferon-alpha