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Defective interferon priming and impaired antiviral responses in a patient with an IRF7 variant and severe influenza.
Thomsen, Michelle M; Jørgensen, Sofie E; Gad, Hans Henrik; Storgaard, Merete; Gjedsted, Jakob; Christiansen, Mette; Hartmann, Rune; Mogensen, Trine H.
Afiliação
  • Thomsen MM; Department of Infectious Diseases, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.
  • Jørgensen SE; Department of Biomedicine, Aarhus University, CF Møllers Alle 6, 8000, Aarhus C, Denmark.
  • Gad HH; Department of Infectious Diseases, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.
  • Storgaard M; Department of Biomedicine, Aarhus University, CF Møllers Alle 6, 8000, Aarhus C, Denmark.
  • Gjedsted J; Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 10, 8000, Aarhus C, Denmark.
  • Christiansen M; Department of Infectious Diseases, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.
  • Hartmann R; Department of Intensive Care, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.
  • Mogensen TH; Department of Clinical Immunology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.
Med Microbiol Immunol ; 208(6): 869-876, 2019 Dec.
Article em En | MEDLINE | ID: mdl-31172279
Influenza infection is common worldwide with many individuals affected each year during epidemics and occasionally pandemics. Previous studies in animal models and a few human cases have established an important role of innate type I and III interferon (IFN) for viral elimination and mounting of antiviral responses. However, genetic and immunological determinants of very severe disseminated influenza virus infection in humans remain incompletely understood. Here, we describe an adult patient with severe influenza virus A (IAV) infection, in whom we identified a rare variant E331V in IFN regulatory factor (IRF)7 by whole-exome sequencing. Examination of patient cells demonstrated a cellular phenotype suggesting functional IRF7 impairment, since priming with IFN was almost abolished and IFN responses to IAV were significantly impaired in patient cells. Moreover, IAV replication was significantly higher in patient cells than in controls. Finally, expression of IRF7 E331V in HEK293 cells demonstrated significantly reduced activation of both IFNA7 and IFNB promoters in a luciferase reporter gene expression assay compared to IRF7 wild type. These findings provide further support for the essential role of IRF7 in amplifying antiviral IFN responses to ensure potent and sustained IFN responses during influenza virus infection in humans.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Interferons / Mutação de Sentido Incorreto / Fator Regulador 7 de Interferon / Influenza Humana / Imunidade Inata / Fatores Imunológicos Idioma: En Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Dinamarca

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Interferons / Mutação de Sentido Incorreto / Fator Regulador 7 de Interferon / Influenza Humana / Imunidade Inata / Fatores Imunológicos Idioma: En Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Dinamarca