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  1. Article ; Online: Influenza A induces lactate formation to inhibit type I IFN in primary human airway epithelium

    Jacob Thyrsted / Jacob Storgaard / Julia Blay-Cadanet / Alexander Heinz / Anne Laugaard Thielke / Stefania Crotta / Frank de Paoli / David Olagnier / Andreas Wack / Karsten Hiller / Anne Louise Hansen / Christian Kanstrup Holm

    iScience, Vol 24, Iss 11, Pp 103300- (2021)

    2021  

    Abstract: Summary: Pathogenic viruses induce metabolic changes in host cells to secure the availability of biomolecules and energy to propagate. Influenza A virus (IAV) and severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) both infect the human airway ... ...

    Abstract Summary: Pathogenic viruses induce metabolic changes in host cells to secure the availability of biomolecules and energy to propagate. Influenza A virus (IAV) and severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) both infect the human airway epithelium and are important human pathogens. The metabolic changes induced by these viruses in a physiologically relevant human model and how this affects innate immune responses to limit viral propagation are not well known. Using an ex vivo model of pseudostratified primary human airway epithelium, we here demonstrate that infection with both IAV and SARS-CoV-2 resulted in distinct metabolic changes including increases in lactate dehydrogenase A (LDHA) expression and LDHA-mediated lactate formation. Interestingly, LDHA regulated both basal and induced mitochondrial anti-viral signaling protein (MAVS)-dependent type I interferon (IFN) responses to promote IAV, but not SARS-CoV-2, replication. Our data demonstrate that LDHA and lactate promote IAV but not SARS-CoV-2 replication by inhibiting MAVS-dependent induction of type I IFN in primary human airway epithelium.
    Keywords Immune response ; Virology ; Metabolomics ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2021-11-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: T cells detect intracellular DNA but fail to induce type I IFN responses

    Randi K Berg / Stine H Rahbek / Emil Kofod-Olsen / Christian K Holm / Jesper Melchjorsen / David G Jensen / Anne Louise Hansen / Louise B Jørgensen / Lars Ostergaard / Martin Tolstrup / Carsten S Larsen / Søren R Paludan / Martin R Jakobsen / Trine H Mogensen

    PLoS ONE, Vol 9, Iss 1, p e

    implications for restriction of HIV replication.

    2014  Volume 84513

    Abstract: HIV infects key cell types of the immune system, most notably macrophages and CD4+ T cells. Whereas macrophages represent an important viral reservoir, activated CD4+ T cells are the most permissive cell types supporting high levels of viral replication. ...

    Abstract HIV infects key cell types of the immune system, most notably macrophages and CD4+ T cells. Whereas macrophages represent an important viral reservoir, activated CD4+ T cells are the most permissive cell types supporting high levels of viral replication. In recent years, it has been appreciated that the innate immune system plays an important role in controlling HIV replication, e.g. via interferon (IFN)-inducible restriction factors. Moreover, innate immune responses are involved in driving chronic immune activation and the pathogenesis of progressive immunodeficiency. Several pattern recognition receptors detecting HIV have been reported, including Toll-like receptor 7 and Retinoic-inducible gene-I, which detects viral RNA. Here we report that human primary T cells fail to induce strong IFN responses, despite the fact that this cell type does express key molecules involved in DNA signaling pathways. We demonstrate that the DNA sensor IFI16 migrates to sites of foreign DNA localization in the cytoplasm and recruits the signaling molecules stimulator of IFN genes and Tank-binding kinase, but this does not result in expression of IFN and IFN-stimulated genes. Importantly, we show that cytosolic DNA fails to affect HIV replication. However, exogenous treatment of activated T cells with type I IFN has the capacity to induce expression of IFN-stimulated genes and suppress HIV replication. Our data suggest the existence of an impaired DNA signaling machinery in T cells, which may prevent this cell type from activating cell-autonomous anti-HIV responses. This phenomenon could contribute to the high permissiveness of CD4+ T cells for HIV-1.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2014-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Author Correction

    David Olagnier / Ensieh Farahani / Jacob Thyrsted / Julia Blay-Cadanet / Angela Herengt / Manja Idorn / Alon Hait / Bruno Hernaez / Alice Knudsen / Marie Beck Iversen / Mirjam Schilling / Sofie E. Jørgensen / Michelle Thomsen / Line S. Reinert / Michael Lappe / Huy-Dung Hoang / Victoria H. Gilchrist / Anne Louise Hansen / Rasmus Ottosen /
    Camilla G. Nielsen / Charlotte Møller / Demi van der Horst / Suraj Peri / Siddharth Balachandran / Jinrong Huang / Martin Jakobsen / Esben B. Svenningsen / Thomas B. Poulsen / Lydia Bartsch / Anne L. Thielke / Yonglun Luo / Tommy Alain / Jan Rehwinkel / Antonio Alcamí / John Hiscott / Trine H. Mogensen / Søren R. Paludan / Christian K. Holm

    Nature Communications, Vol 11, Iss 1, Pp 1-

    SARS-CoV2-mediated suppression of NRF2-signaling reveals potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate

    2020  Volume 1

    Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    Abstract An amendment to this paper has been published and can be accessed via a link at the top of the paper.
    Keywords Science ; Q
    Language English
    Publishing date 2020-10-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: SARS-CoV2-mediated suppression of NRF2-signaling reveals potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate

    David Olagnier / Ensieh Farahani / Jacob Thyrsted / Julia Blay-Cadanet / Angela Herengt / Manja Idorn / Alon Hait / Bruno Hernaez / Alice Knudsen / Marie Beck Iversen / Mirjam Schilling / Sofie E. Jørgensen / Michelle Thomsen / Line S. Reinert / Michael Lappe / Huy-Dung Hoang / Victoria H. Gilchrist / Anne Louise Hansen / Rasmus Ottosen /
    Camilla G. Nielsen / Charlotte Møller / Demi van der Horst / Suraj Peri / Siddharth Balachandran / Jinrong Huang / Martin Jakobsen / Esben B. Svenningsen / Thomas B. Poulsen / Lydia Bartsch / Anne L. Thielke / Yonglun Luo / Tommy Alain / Jan Rehwinkel / Antonio Alcamí / John Hiscott / Trine Mogensen / Søren R. Paludan / Christian K. Holm

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 12

    Abstract: Viral infections usually cause disease through direct cytopathogenic effects and excessive inflammatory responses. Here, Olagnier et al. show that two NRF2 agonists, 4-OI and DMF, possess broad IFN-independent antiviral activity and decrease host ... ...

    Abstract Viral infections usually cause disease through direct cytopathogenic effects and excessive inflammatory responses. Here, Olagnier et al. show that two NRF2 agonists, 4-OI and DMF, possess broad IFN-independent antiviral activity and decrease host inflammatory response to SARS-CoV-2 infection.
    Keywords Science ; Q ; covid19
    Language English
    Publishing date 2020-10-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: SARS-CoV2-mediated suppression of NRF2-signaling reveals potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate

    David Olagnier / Ensieh Farahani / Jacob Thyrsted / Julia Blay-Cadanet / Angela Herengt / Manja Idorn / Alon Hait / Bruno Hernaez / Alice Knudsen / Marie Beck Iversen / Mirjam Schilling / Sofie E. Jørgensen / Michelle Thomsen / Line S. Reinert / Michael Lappe / Huy-Dung Hoang / Victoria H. Gilchrist / Anne Louise Hansen / Rasmus Ottosen /
    Camilla G. Nielsen / Charlotte Møller / Demi van der Horst / Suraj Peri / Siddharth Balachandran / Jinrong Huang / Martin Jakobsen / Esben B. Svenningsen / Thomas B. Poulsen / Lydia Bartsch / Anne L. Thielke / Yonglun Luo / Tommy Alain / Jan Rehwinkel / Antonio Alcamí / John Hiscott / Trine H. Mogensen / Søren R. Paludan / Christian K. Holm

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 12

    Abstract: Viral infections usually cause disease through direct cytopathogenic effects and excessive inflammatory responses. Here, Olagnier et al. show that two NRF2 agonists, 4-OI and DMF, possess broad IFN-independent antiviral activity and decrease host ... ...

    Abstract Viral infections usually cause disease through direct cytopathogenic effects and excessive inflammatory responses. Here, Olagnier et al. show that two NRF2 agonists, 4-OI and DMF, possess broad IFN-independent antiviral activity and decrease host inflammatory response to SARS-CoV-2 infection.
    Keywords Science ; Q
    Language English
    Publishing date 2020-10-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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  6. Article ; Online: Author Correction

    David Olagnier / Ensieh Farahani / Jacob Thyrsted / Julia Blay-Cadanet / Angela Herengt / Manja Idorn / Alon Hait / Bruno Hernaez / Alice Knudsen / Marie Beck Iversen / Mirjam Schilling / Sofie E. Jørgensen / Michelle Thomsen / Line S. Reinert / Michael Lappe / Huy-Dung Hoang / Victoria H. Gilchrist / Anne Louise Hansen / Rasmus Ottosen /
    Camilla G. Nielsen / Charlotte Møller / Demi van der Horst / Suraj Peri / Siddharth Balachandran / Jinrong Huang / Martin Jakobsen / Esben B. Svenningsen / Thomas B. Poulsen / Lydia Bartsch / Anne L. Thielke / Yonglun Luo / Tommy Alain / Jan Rehwinkel / Antonio Alcamí / John Hiscott / Trine H. Mogensen / Søren R. Paludan / Christian K. Holm

    Nature Communications, Vol 11, Iss 1, Pp 1-

    SARS-CoV2-mediated suppression of NRF2-signaling reveals potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate

    2020  Volume 1

    Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    Abstract An amendment to this paper has been published and can be accessed via a link at the top of the paper.
    Keywords Science ; Q
    Language English
    Publishing date 2020-10-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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  7. Article ; Online: Influenza A virus targets a cGAS-independent STING pathway that controls enveloped RNA viruses

    Christian K. Holm / Stine H. Rahbek / Hans Henrik Gad / Rasmus O. Bak / Martin R. Jakobsen / Zhaozaho Jiang / Anne Louise Hansen / Simon K. Jensen / Chenglong Sun / Martin K. Thomsen / Anders Laustsen / Camilla G. Nielsen / Kasper Severinsen / Yingluo Xiong / Dara L. Burdette / Veit Hornung / Robert Jan Lebbink / Mogens Duch / Katherine A. Fitzgerald /
    Shervin Bahrami / Jakob Giehm Mikkelsen / Rune Hartmann / Søren R. Paludan

    Nature Communications, Vol 7, Iss 1, Pp 1-

    2016  Volume 9

    Abstract: Stimulator of interferon genes (STING) is known to be involved in defence against DNA viruses, but its role in the control of RNA viruses remains poorly explored. Here the authors show that STING participates in an innate immune response to RNA virus ... ...

    Abstract Stimulator of interferon genes (STING) is known to be involved in defence against DNA viruses, but its role in the control of RNA viruses remains poorly explored. Here the authors show that STING participates in an innate immune response to RNA virus infection in a cGAS-independent manner.
    Keywords Science ; Q
    Language English
    Publishing date 2016-02-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Nrf2 negatively regulates STING indicating a link between antiviral sensing and metabolic reprogramming

    David Olagnier / Aske M. Brandtoft / Camilla Gunderstofte / Nikolaj L. Villadsen / Christian Krapp / Anne L. Thielke / Anders Laustsen / Suraj Peri / Anne Louise Hansen / Lene Bonefeld / Jacob Thyrsted / Victor Bruun / Marie B. Iversen / Lin Lin / Virginia M. Artegoitia / Chenhe Su / Long Yang / Rongtuan Lin / Siddharth Balachandran /
    Yonglun Luo / Mette Nyegaard / Bernadette Marrero / Raphaela Goldbach-Mansky / Mona Motwani / Dylan G. Ryan / Katherine A. Fitzgerald / Luke A. O’Neill / Anne K. Hollensen / Christian K. Damgaard / Frank v. de Paoli / Hanne C. Bertram / Martin R. Jakobsen / Thomas B. Poulsen / Christian K. Holm

    Nature Communications, Vol 9, Iss 1, Pp 1-

    2018  Volume 13

    Abstract: Understanding how regulators of inflammation affect nucleic acid sensing is important for targeting research against inflammatory diseases and conditions. Here, the authors identify Nrf2 as an important negative regulator of STING and suggest a link ... ...

    Abstract Understanding how regulators of inflammation affect nucleic acid sensing is important for targeting research against inflammatory diseases and conditions. Here, the authors identify Nrf2 as an important negative regulator of STING and suggest a link between metabolic reprogramming and antiviral cytosolic DNA sensing in human cells.
    Keywords Science ; Q
    Language English
    Publishing date 2018-08-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Nrf2 negatively regulates STING indicating a link between antiviral sensing and metabolic reprogramming

    David Olagnier / Aske M. Brandtoft / Camilla Gunderstofte / Nikolaj L. Villadsen / Christian Krapp / Anne L. Thielke / Anders Laustsen / Suraj Peri / Anne Louise Hansen / Lene Bonefeld / Jacob Thyrsted / Victor Bruun / Marie B. Iversen / Lin Lin / Virginia M. Artegoitia / Chenhe Su / Long Yang / Rongtuan Lin / Siddharth Balachandran /
    Yonglun Luo / Mette Nyegaard / Bernadette Marrero / Raphaela Goldbach-Mansky / Mona Motwani / Dylan G. Ryan / Katherine A. Fitzgerald / Luke A. O’Neill / Anne K. Hollensen / Christian K. Damgaard / Frank v. de Paoli / Hanne C. Bertram / Martin R. Jakobsen / Thomas B. Poulsen / Christian K. Holm

    Nature Communications, Vol 9, Iss 1, Pp 1-

    2018  Volume 13

    Abstract: Understanding how regulators of inflammation affect nucleic acid sensing is important for targeting research against inflammatory diseases and conditions. Here, the authors identify Nrf2 as an important negative regulator of STING and suggest a link ... ...

    Abstract Understanding how regulators of inflammation affect nucleic acid sensing is important for targeting research against inflammatory diseases and conditions. Here, the authors identify Nrf2 as an important negative regulator of STING and suggest a link between metabolic reprogramming and antiviral cytosolic DNA sensing in human cells.
    Keywords Science ; Q
    Language English
    Publishing date 2018-08-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

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