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Defective interferon priming and impaired antiviral responses in a patient with an IRF7 variant and severe influenza

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Harvard

Thomsen, MM, Jørgensen, SE, Gad, HH, Storgaard, M, Gjedsted, J, Christiansen, M, Hartmann, R & Mogensen, TH 2019, 'Defective interferon priming and impaired antiviral responses in a patient with an IRF7 variant and severe influenza', Medical Microbiology and Immunology, bind 208, nr. 6, s. 869-876. https://doi.org/10.1007/s00430-019-00623-8

APA

Thomsen, M. M., Jørgensen, S. E., Gad, H. H., Storgaard, M., Gjedsted, J., Christiansen, M., Hartmann, R., & Mogensen, T. H. (2019). Defective interferon priming and impaired antiviral responses in a patient with an IRF7 variant and severe influenza. Medical Microbiology and Immunology, 208(6), 869-876. https://doi.org/10.1007/s00430-019-00623-8

CBE

MLA

Vancouver

Author

Thomsen, Michelle M ; Jørgensen, Sofie E ; Gad, Hans Henrik ; Storgaard, Merete ; Gjedsted, Jakob ; Christiansen, Mette ; Hartmann, Rune ; Mogensen, Trine H. / Defective interferon priming and impaired antiviral responses in a patient with an IRF7 variant and severe influenza. I: Medical Microbiology and Immunology. 2019 ; Bind 208, Nr. 6. s. 869-876.

Bibtex

@article{f1f47cbd339048a7a04d7184852394bb,
title = "Defective interferon priming and impaired antiviral responses in a patient with an IRF7 variant and severe influenza",
abstract = "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.",
author = "Thomsen, {Michelle M} and J{\o}rgensen, {Sofie E} and Gad, {Hans Henrik} and Merete Storgaard and Jakob Gjedsted and Mette Christiansen and Rune Hartmann and Mogensen, {Trine H}",
year = "2019",
month = dec,
doi = "10.1007/s00430-019-00623-8",
language = "English",
volume = "208",
pages = "869--876",
journal = "Medical Microbiology and Immunology",
issn = "0300-8584",
publisher = "Springer",
number = "6",

}

RIS

TY - JOUR

T1 - Defective interferon priming and impaired antiviral responses in a patient with an IRF7 variant and severe influenza

AU - Thomsen, Michelle M

AU - Jørgensen, Sofie E

AU - Gad, Hans Henrik

AU - Storgaard, Merete

AU - Gjedsted, Jakob

AU - Christiansen, Mette

AU - Hartmann, Rune

AU - Mogensen, Trine H

PY - 2019/12

Y1 - 2019/12

N2 - 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.

AB - 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.

U2 - 10.1007/s00430-019-00623-8

DO - 10.1007/s00430-019-00623-8

M3 - Journal article

C2 - 31172279

VL - 208

SP - 869

EP - 876

JO - Medical Microbiology and Immunology

JF - Medical Microbiology and Immunology

SN - 0300-8584

IS - 6

ER -

ID: 59055422