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  1. Article ; Online: Viral recognition and the antiviral interferon response.

    Dalskov, Louise / Gad, Hans Henrik / Hartmann, Rune

    The EMBO journal

    2023  Volume 42, Issue 14, Page(s) e112907

    Abstract: Interferons (IFNs) are antiviral cytokines that play a key role in the innate immune response to viral infections. In response to viral stimuli, cells produce and release interferons, which then act on neighboring cells to induce the transcription of ... ...

    Abstract Interferons (IFNs) are antiviral cytokines that play a key role in the innate immune response to viral infections. In response to viral stimuli, cells produce and release interferons, which then act on neighboring cells to induce the transcription of hundreds of genes. Many of these gene products either combat the viral infection directly, e.g., by interfering with viral replication, or help shape the following immune response. Here, we review how viral recognition leads to the production of different types of IFNs and how this production differs in spatial and temporal manners. We then continue to describe how these IFNs play different roles in the ensuing immune response depending on when and where they are produced or act during an infection.
    MeSH term(s) Humans ; Interferons ; Interferon Regulatory Factor-3/metabolism ; Antiviral Agents/pharmacology ; Immunity, Innate ; Cytokines ; Virus Diseases/drug therapy
    Chemical Substances Interferons (9008-11-1) ; Interferon Regulatory Factor-3 ; Antiviral Agents ; Cytokines
    Language English
    Publishing date 2023-06-27
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 586044-1
    ISSN 1460-2075 ; 0261-4189
    ISSN (online) 1460-2075
    ISSN 0261-4189
    DOI 10.15252/embj.2022112907
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  2. Article ; Online: Characterization of distinct molecular interactions responsible for IRF3 and IRF7 phosphorylation and subsequent dimerization.

    Dalskov, Louise / Narita, Ryo / Andersen, Line L / Jensen, Nanna / Assil, Sonia / Kristensen, Kennith H / Mikkelsen, Jacob G / Fujita, Takashi / Mogensen, Trine H / Paludan, Søren R / Hartmann, Rune

    Nucleic acids research

    2020  Volume 48, Issue 20, Page(s) 11421–11433

    Abstract: IRF3 and IRF7 are critical transcription factors in the innate immune response. Their activation is controlled by phosphorylation events, leading to the formation of homodimers that are transcriptionally active. Phosphorylation occurs when IRF3 is ... ...

    Abstract IRF3 and IRF7 are critical transcription factors in the innate immune response. Their activation is controlled by phosphorylation events, leading to the formation of homodimers that are transcriptionally active. Phosphorylation occurs when IRF3 is recruited to adaptor proteins via a positively charged surface within the regulatory domain of IRF3. This positively charged surface also plays a crucial role in forming the active homodimer by interacting with the phosphorylated sites stabilizing the homodimer. Here, we describe a distinct molecular interaction that is responsible for adaptor docking and hence phosphorylation as well as a separate interaction responsible for the formation of active homodimer. We then demonstrate that IRF7 can be activated by both MAVS and STING in a manner highly similar to that of IRF3 but with one key difference. Regulation of IRF7 appears more tightly controlled; while a single phosphorylation event is sufficient to activate IRF3, at least two phosphorylation events are required for IRF7 activation.
    MeSH term(s) Adaptor Proteins, Signal Transducing/chemistry ; Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Dimerization ; Genes, Reporter ; HEK293 Cells ; Humans ; Immunity, Innate ; Interferon Regulatory Factor-3/chemistry ; Interferon Regulatory Factor-3/genetics ; Interferon Regulatory Factor-3/metabolism ; Interferon Regulatory Factor-7/genetics ; Interferon Regulatory Factor-7/metabolism ; Membrane Proteins/chemistry ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Phosphorylation ; Protein Binding/genetics ; Protein Serine-Threonine Kinases/metabolism ; Signal Transduction/genetics ; Signal Transduction/immunology ; NF-kappaB-Inducing Kinase
    Chemical Substances Adaptor Proteins, Signal Transducing ; IRF3 protein, human ; IRF7 protein, human ; Interferon Regulatory Factor-3 ; Interferon Regulatory Factor-7 ; MAVS protein, human ; Membrane Proteins ; STING1 protein, human ; Protein Serine-Threonine Kinases (EC 2.7.11.1)
    Language English
    Publishing date 2020-11-17
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 186809-3
    ISSN 1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
    ISSN (online) 1362-4962 ; 1362-4954
    ISSN 0301-5610 ; 0305-1048
    DOI 10.1093/nar/gkaa873
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  3. Article ; Online: SARS-CoV-2 evades immune detection in alveolar macrophages.

    Dalskov, Louise / Møhlenberg, Michelle / Thyrsted, Jacob / Blay-Cadanet, Julia / Poulsen, Ebbe Toftgaard / Folkersen, Birgitte Holst / Skaarup, Søren Helbo / Olagnier, David / Reinert, Line / Enghild, Jan Johannes / Hoffmann, Hans Jürgen / Holm, Christian Kanstrup / Hartmann, Rune

    EMBO reports

    2020  Volume 21, Issue 12, Page(s) e51252

    Abstract: Respiratory infections, like the current COVID-19 pandemic, target epithelial cells in the respiratory tract. Alveolar macrophages (AMs) are tissue-resident macrophages located within the lung. They play a key role in the early phases of an immune ... ...

    Abstract Respiratory infections, like the current COVID-19 pandemic, target epithelial cells in the respiratory tract. Alveolar macrophages (AMs) are tissue-resident macrophages located within the lung. They play a key role in the early phases of an immune response to respiratory viruses. AMs are likely the first immune cells to encounter SARS-CoV-2 during an infection, and their reaction to the virus will have a profound impact on the outcome of the infection. Interferons (IFNs) are antiviral cytokines and among the first cytokines produced upon viral infection. In this study, AMs from non-infectious donors are challenged with SARS-CoV-2. We demonstrate that challenged AMs are incapable of sensing SARS-CoV-2 and of producing an IFN response in contrast to other respiratory viruses, like influenza A virus and Sendai virus, which trigger a robust IFN response. The absence of IFN production in AMs upon challenge with SARS-CoV-2 could explain the initial asymptotic phase observed during COVID-19 and argues against AMs being the sources of pro-inflammatory cytokines later during infection.
    MeSH term(s) Antiviral Agents/immunology ; COVID-19/immunology ; COVID-19/virology ; Cells, Cultured ; Cytokines/immunology ; Epithelial Cells/immunology ; Epithelial Cells/virology ; Humans ; Immune Evasion ; Interferon Type I/immunology ; Lung/immunology ; Lung/virology ; Macrophages, Alveolar/immunology ; Macrophages, Alveolar/virology ; Pandemics ; SARS-CoV-2/immunology
    Chemical Substances Antiviral Agents ; Cytokines ; Interferon Type I
    Keywords covid19
    Language English
    Publishing date 2020-10-28
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2020896-0
    ISSN 1469-3178 ; 1469-221X
    ISSN (online) 1469-3178
    ISSN 1469-221X
    DOI 10.15252/embr.202051252
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Two cGAS-like receptors induce antiviral immunity in Drosophila.

    Holleufer, Andreas / Winther, Kasper Grønbjerg / Gad, Hans Henrik / Ai, Xianlong / Chen, Yuqiang / Li, Lihua / Wei, Ziming / Deng, Huimin / Liu, Jiyong / Frederiksen, Ninna Ahlmann / Simonsen, Bine / Andersen, Line Lykke / Kleigrewe, Karin / Dalskov, Louise / Pichlmair, Andreas / Cai, Hua / Imler, Jean-Luc / Hartmann, Rune

    Nature

    2021  Volume 597, Issue 7874, Page(s) 114–118

    Abstract: In mammals, cyclic GMP-AMP (cGAMP) synthase (cGAS) produces the cyclic dinucleotide 2'3'-cGAMP in response to cytosolic DNA and this triggers an antiviral immune response. cGAS belongs to a large family of cGAS/DncV-like nucleotidyltransferases that is ... ...

    Abstract In mammals, cyclic GMP-AMP (cGAMP) synthase (cGAS) produces the cyclic dinucleotide 2'3'-cGAMP in response to cytosolic DNA and this triggers an antiviral immune response. cGAS belongs to a large family of cGAS/DncV-like nucleotidyltransferases that is present in both prokaryotes
    MeSH term(s) Amino Acid Sequence ; Animals ; Cell Line ; Drosophila Proteins/metabolism ; Drosophila melanogaster/immunology ; Drosophila melanogaster/metabolism ; Drosophila melanogaster/virology ; Female ; Humans ; Immunity, Innate/genetics ; Immunity, Innate/immunology ; Ligands ; Male ; Membrane Proteins/metabolism ; Models, Molecular ; NF-kappa B/metabolism ; Nucleotides, Cyclic/metabolism ; Nucleotidyltransferases/classification ; Nucleotidyltransferases/deficiency ; Nucleotidyltransferases/immunology ; Nucleotidyltransferases/metabolism ; RNA, Double-Stranded/analysis ; RNA, Double-Stranded/immunology ; RNA, Double-Stranded/metabolism ; Receptors, Pattern Recognition/classification ; Receptors, Pattern Recognition/deficiency ; Receptors, Pattern Recognition/immunology ; Receptors, Pattern Recognition/metabolism ; Viruses/immunology
    Chemical Substances Drosophila Proteins ; Ligands ; Membrane Proteins ; NF-kappa B ; Nucleotides, Cyclic ; RNA, Double-Stranded ; Receptors, Pattern Recognition ; STING1 protein, human ; Sting protein, Drosophila ; cyclic guanosine monophosphate-adenosine monophosphate ; Nucleotidyltransferases (EC 2.7.7.-)
    Language English
    Publishing date 2021-07-14
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/s41586-021-03800-z
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    Zs.MO 244: Show issues

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  5. Article: SARS-CoV-2 evades immune detection in alveolar macrophages

    Dalskov, Louise / Møhlenberg, Michelle / Thyrsted, Jacob / Blay-Cadanet, Julia / Poulsen, Ebbe Toftgaard / Folkersen, Birgitte Holst / Skaarup, Søren Helbo / Olagnier, David / Reinert, Line / Enghild, Jan Johannes / Hoffmann, Hans Jürgen / Holm, Christian Kanstrup / Hartmann, Rune

    EMBO Rep

    Abstract: Respiratory infections, like the current COVID-19 pandemic, target epithelial cells in the respiratory tract. Alveolar macrophages (AMs) are tissue-resident macrophages located within the lung. They play a key role in the early phases of an immune ... ...

    Abstract Respiratory infections, like the current COVID-19 pandemic, target epithelial cells in the respiratory tract. Alveolar macrophages (AMs) are tissue-resident macrophages located within the lung. They play a key role in the early phases of an immune response to respiratory viruses. AMs are likely the first immune cells to encounter SARS-CoV-2 during an infection, and their reaction to the virus will have a profound impact on the outcome of the infection. Interferons (IFNs) are antiviral cytokines and among the first cytokines produced upon viral infection. In this study, AMs from non-infectious donors are challenged with SARS-CoV-2. We demonstrate that challenged AMs are incapable of sensing SARS-CoV-2 and of producing an IFN response in contrast to other respiratory viruses, like influenza A virus and Sendai virus, which trigger a robust IFN response. The absence of IFN production in AMs upon challenge with SARS-CoV-2 could explain the initial asymptotic phase observed during COVID-19 and argues against AMs being the sources of pro-inflammatory cytokines later during infection.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #895751
    Database COVID19

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  6. Article ; Online: SARS-CoV-2 evades immune detection in alveolar macrophages

    Dalskov, Louise / Møhlenberg, Michelle / Thyrsted, Jacob / Blay-Cadanet, Julia / Poulsen, Ebbe Toftgaard / Folkersen, Birgitte Holst / Skaarup, Søren Helbo / Olagnier, David / Reinert, Line / Enghild, Jan Johannes / Hoffmann, Hans Jürgen / Holm, Christian Kanstrup / Hartmann, Rune

    Dalskov , L , Møhlenberg , M , Thyrsted , J , Blay-Cadanet , J , Poulsen , E T , Folkersen , B H , Skaarup , S H , Olagnier , D , Reinert , L , Enghild , J J , Hoffmann , H J , Holm , C K & Hartmann , R 2020 , ' SARS-CoV-2 evades immune detection in alveolar macrophages ' , EMBO Reports , pp. e51252 . https://doi.org/10.15252/embr.202051252

    2020  

    Abstract: Respiratory infections, like the current COVID-19 pandemic, target epithelial cells in the respiratory tract. Alveolar macrophages (AMs) are tissue-resident macrophages located within the lung. They play a key role in the early phases of an immune ... ...

    Abstract Respiratory infections, like the current COVID-19 pandemic, target epithelial cells in the respiratory tract. Alveolar macrophages (AMs) are tissue-resident macrophages located within the lung. They play a key role in the early phases of an immune response to respiratory viruses. AMs are likely the first immune cells to encounter SARS-CoV-2 during an infection, and their reaction to the virus will have a profound impact on the outcome of the infection. Interferons (IFNs) are antiviral cytokines and among the first cytokines produced upon viral infection. In this study, AMs from non-infectious donors are challenged with SARS-CoV-2. We demonstrate that challenged AMs are incapable of sensing SARS-CoV-2 and of producing an IFN response in contrast to other respiratory viruses, like influenza A virus and Sendai virus, which trigger a robust IFN response. The absence of IFN production in AMs upon challenge with SARS-CoV-2 could explain the initial asymptotic phase observed during COVID-19 and argues against AMs being the sources of pro-inflammatory cytokines later during infection.
    Keywords covid19
    Subject code 570
    Language English
    Publishing date 2020-10-28
    Publishing country dk
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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