The HIF transcription network exerts innate antiviral activity in neurons and limits brain inflammation
Summary: Pattern recognition receptors (PRRs) induce host defense but can also induce exacerbated inflammatory responses. This raises the question of whether other mechanisms are also involved in early host defense. Using transcriptome analysis of disrupted transcripts in herpes simplex virus (HSV)-...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-02-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724001207 |
| _version_ | 1827338906975076352 |
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| author | Ensieh Farahani Line S. Reinert Ryo Narita Manutea C. Serrero Morten Kelder Skouboe Demi van der Horst Sonia Assil Baocun Zhang Marie B. Iversen Eugenio Gutierrez Hossein Hazrati Mogens Johannsen David Olagnier Reiner Kunze Mark Denham Trine H. Mogensen Michael Lappe Søren R. Paludan |
| author_facet | Ensieh Farahani Line S. Reinert Ryo Narita Manutea C. Serrero Morten Kelder Skouboe Demi van der Horst Sonia Assil Baocun Zhang Marie B. Iversen Eugenio Gutierrez Hossein Hazrati Mogens Johannsen David Olagnier Reiner Kunze Mark Denham Trine H. Mogensen Michael Lappe Søren R. Paludan |
| author_sort | Ensieh Farahani |
| collection | DOAJ |
| description | Summary: Pattern recognition receptors (PRRs) induce host defense but can also induce exacerbated inflammatory responses. This raises the question of whether other mechanisms are also involved in early host defense. Using transcriptome analysis of disrupted transcripts in herpes simplex virus (HSV)-infected cells, we find that HSV infection disrupts the hypoxia-inducible factor (HIF) transcription network in neurons and epithelial cells. Importantly, HIF activation leads to control of HSV replication. Mechanistically, HIF activation induces autophagy, which is essential for antiviral activity. HSV-2 infection in vivo leads to hypoxia in CNS neurons, and mice with neuron-specific HIF1/2α deficiency exhibit elevated viral load and augmented PRR signaling and inflammatory gene expression in the CNS after HSV-2 infection. Data from human stem cell-derived neuron and microglia cultures show that HIF also exerts antiviral and inflammation-restricting activity in human CNS cells. Collectively, the HIF transcription factor system senses virus-induced hypoxic stress to induce cell-intrinsic antiviral responses and limit inflammation. |
| first_indexed | 2024-03-07T19:42:24Z |
| format | Article |
| id | doaj.art-44f664b9af4a437aa62a40c3c3077e62 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-07T19:42:24Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-44f664b9af4a437aa62a40c3c3077e622024-02-29T05:18:59ZengElsevierCell Reports2211-12472024-02-01432113792The HIF transcription network exerts innate antiviral activity in neurons and limits brain inflammationEnsieh Farahani0Line S. Reinert1Ryo Narita2Manutea C. Serrero3Morten Kelder Skouboe4Demi van der Horst5Sonia Assil6Baocun Zhang7Marie B. Iversen8Eugenio Gutierrez9Hossein Hazrati10Mogens Johannsen11David Olagnier12Reiner Kunze13Mark Denham14Trine H. Mogensen15Michael Lappe16Søren R. Paludan17Department of Biomedicine, Aarhus University, Aarhus, DenmarkDepartment of Biomedicine, Aarhus University, Aarhus, Denmark; Center for Immunology of Viral Infections, Aarhus University, Aarhus, DenmarkDepartment of Biomedicine, Aarhus University, Aarhus, Denmark; Center for Immunology of Viral Infections, Aarhus University, Aarhus, DenmarkDepartment of Biomedicine, Aarhus University, Aarhus, Denmark; Center for Immunology of Viral Infections, Aarhus University, Aarhus, DenmarkDepartment of Biomedicine, Aarhus University, Aarhus, Denmark; Center for Immunology of Viral Infections, Aarhus University, Aarhus, Denmark; Department of Infectious Diseases, Aarhus University Hospital, Aarhus, DenmarkDepartment of Biomedicine, Aarhus University, Aarhus, Denmark; Center for Immunology of Viral Infections, Aarhus University, Aarhus, DenmarkDepartment of Biomedicine, Aarhus University, Aarhus, Denmark; Center for Immunology of Viral Infections, Aarhus University, Aarhus, DenmarkDepartment of Biomedicine, Aarhus University, Aarhus, Denmark; Center for Immunology of Viral Infections, Aarhus University, Aarhus, DenmarkDepartment of Biomedicine, Aarhus University, Aarhus, Denmark; Center for Immunology of Viral Infections, Aarhus University, Aarhus, DenmarkCenter of Functionally Integrative Neuroscience, Aarhus University, Aarhus, DenmarkDepartment of Biomedicine, Aarhus University, Aarhus, Denmark; Center for Immunology of Viral Infections, Aarhus University, Aarhus, Denmark; Department of Forensic Science, Aarhus University, Aarhus, DenmarkDepartment of Forensic Science, Aarhus University, Aarhus, DenmarkDepartment of Biomedicine, Aarhus University, Aarhus, Denmark; Center for Immunology of Viral Infections, Aarhus University, Aarhus, DenmarkInstitute of Physiology and Pathophysiology, Heidelberg University, Heidelberg, GermanyDepartment of Biomedicine, Aarhus University, Aarhus, Denmark; Danish Research Institute of Translational Neuroscience, Nordic EMBL Partnership for Molecular Medicine, Aarhus University, Aarhus, DenmarkDepartment of Biomedicine, Aarhus University, Aarhus, Denmark; Center for Immunology of Viral Infections, Aarhus University, Aarhus, Denmark; Department of Infectious Diseases, Aarhus University Hospital, Aarhus, DenmarkDepartment of Molecular Medicine (MOMA), Aarhus University Hospital, Aarhus, Denmark; CONNECT - Center for Clinical and Genomic Data, Aarhus University Hospital, Aarhus, DenmarkDepartment of Biomedicine, Aarhus University, Aarhus, Denmark; Center for Immunology of Viral Infections, Aarhus University, Aarhus, Denmark; Corresponding authorSummary: Pattern recognition receptors (PRRs) induce host defense but can also induce exacerbated inflammatory responses. This raises the question of whether other mechanisms are also involved in early host defense. Using transcriptome analysis of disrupted transcripts in herpes simplex virus (HSV)-infected cells, we find that HSV infection disrupts the hypoxia-inducible factor (HIF) transcription network in neurons and epithelial cells. Importantly, HIF activation leads to control of HSV replication. Mechanistically, HIF activation induces autophagy, which is essential for antiviral activity. HSV-2 infection in vivo leads to hypoxia in CNS neurons, and mice with neuron-specific HIF1/2α deficiency exhibit elevated viral load and augmented PRR signaling and inflammatory gene expression in the CNS after HSV-2 infection. Data from human stem cell-derived neuron and microglia cultures show that HIF also exerts antiviral and inflammation-restricting activity in human CNS cells. Collectively, the HIF transcription factor system senses virus-induced hypoxic stress to induce cell-intrinsic antiviral responses and limit inflammation.http://www.sciencedirect.com/science/article/pii/S2211124724001207CP: ImmunologyCP: Microbiology |
| spellingShingle | Ensieh Farahani Line S. Reinert Ryo Narita Manutea C. Serrero Morten Kelder Skouboe Demi van der Horst Sonia Assil Baocun Zhang Marie B. Iversen Eugenio Gutierrez Hossein Hazrati Mogens Johannsen David Olagnier Reiner Kunze Mark Denham Trine H. Mogensen Michael Lappe Søren R. Paludan The HIF transcription network exerts innate antiviral activity in neurons and limits brain inflammation Cell Reports CP: Immunology CP: Microbiology |
| title | The HIF transcription network exerts innate antiviral activity in neurons and limits brain inflammation |
| title_full | The HIF transcription network exerts innate antiviral activity in neurons and limits brain inflammation |
| title_fullStr | The HIF transcription network exerts innate antiviral activity in neurons and limits brain inflammation |
| title_full_unstemmed | The HIF transcription network exerts innate antiviral activity in neurons and limits brain inflammation |
| title_short | The HIF transcription network exerts innate antiviral activity in neurons and limits brain inflammation |
| title_sort | hif transcription network exerts innate antiviral activity in neurons and limits brain inflammation |
| topic | CP: Immunology CP: Microbiology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724001207 |
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