Academic Journal
Retinoic Acid Inducible Gene I and Protein Kinase R, but Not Stress Granules, Mediate the Proinflammatory Response to Yellow Fever Virus
| العنوان: | Retinoic Acid Inducible Gene I and Protein Kinase R, but Not Stress Granules, Mediate the Proinflammatory Response to Yellow Fever Virus |
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| المؤلفون: | Beauclair, Guillaume, Streicher, Felix, Chazal, Maxime, Bruni, Daniela, Lesage, Sarah, Gracias, Ségolène, Bourgeau, Salomé, Sinigaglia, Laura, Fujita, Takashi, Meurs, Eliane, Tangy, Frédéric, Jouvenet, Nolwenn |
| المساهمون: | Virologie (CNRS - UMR3569), Institut Pasteur Paris (IP)-Centre National de la Recherche Scientifique (CNRS), Université Paris Cité (UPCité), Génomique virale et vaccination, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique EHESP (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Kyoto University, Hépacivirus et Immunité innée, ANR-16-CE15002501, Agence Nationale de la Recherche, ANR-16-CE15-0025,Viro-Storm,Mécanismes de production incontrôlée de cytokines au cours de l'infection virale(2016) |
| المصدر: | ISSN: 0022-538X. |
| بيانات النشر: | HAL CCSD American Society for Microbiology |
| سنة النشر: | 2020 |
| المجموعة: | Université de Rennes 1: Publications scientifiques (HAL) |
| مصطلحات موضوعية: | cytokines, flavivirus, innate immunity, interferons, liver inflammation, pattern recognition receptors, stress granules, yellow fever virus, MESH: Adaptor Proteins, Signal Transducing, MESH: Animals, MESH: eIF-2 Kinase, MESH: Cell Line, MESH: DEAD Box Protein 58, Tumor, MESH: Cytokines, MESH: DNA Helicases, MESH: Hepatocytes, MESH: Gene Knockdown Techniques, MESH: Haplorhini, MESH: Humans, MESH: RNA Recognition Motif Proteins, MESH: Poly-ADP-Ribose Binding Proteins, MESH: RNA Helicases, MESH: RNA, Small Interfering, MESH: T-Cell Intracellular Antigen-1, Viral, MESH: RNA-Binding Proteins, MESH: Transcriptome |
| الوصف: | International audience ; Yellow fever virus (YFV) is an RNA virus primarily targeting the liver. Severe YF cases are responsible for hemorrhagic fever, plausibly precipitated by excessive proinflammatory cytokine response. Pathogen recognition receptors (PRRs), such as the cytoplasmic retinoic acid inducible gene I (RIG-I)-like receptors (RLRs), and the viral RNA sensor protein kinase R (PKR), are known to initiate a proinflammatory response upon recognition of viral genomes. Here, we sought to reveal the main determinants responsible for the acute cytokine expression occurring in human hepatocytes following YFV infection. Using a RIG-I-defective human hepatoma cell line, we found that RIG-I largely contributes to cytokine secretion upon YFV infection. In infected RIG-I-proficient hepatoma cells, RIG-I was localized in stress granules. These granules are large aggregates of stalled translation preinitiation complexes known to concentrate RLRs and PKR and are so far recognized as hubs orchestrating RNA virus sensing. Stable knockdown of PKR in hepatoma cells revealed that PKR contributes to both stress granule formation and cytokine induction upon YFV infection. However, stress granule disruption did not affect the cytokine response to YFV infection, as assessed by small interfering RNA (siRNA)-knockdown-mediated inhibition of stress granule assembly. Finally, no viral RNA was detected in stress granules using a fluorescence in situ hybridization approach coupled with immunofluorescence. Our findings suggest that both RIG-I and PKR mediate proinflammatory cytokine induction in YFV-infected hepatocytes, in a stress granule-independent manner. Therefore, by showing the uncoupling of the cytokine response from the stress granule formation, our model challenges the current view in which stress granules are required for the mounting of the acute antiviral response. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/32878892; hal-03102115; https://hal.science/hal-03102115; https://hal.science/hal-03102115/document; https://hal.science/hal-03102115/file/beauclair-et-al-2020-retinoic-acid-inducible-gene-i-and-protein-kinase-r-but-not-stress-granules-mediate-the.pdf; PUBMED: 32878892; PUBMEDCENTRAL: PMC7592215 |
| DOI: | 10.1128/JVI.00403-20 |
| الاتاحة: | https://hal.science/hal-03102115 https://hal.science/hal-03102115/document https://hal.science/hal-03102115/file/beauclair-et-al-2020-retinoic-acid-inducible-gene-i-and-protein-kinase-r-but-not-stress-granules-mediate-the.pdf https://doi.org/10.1128/JVI.00403-20 |
| Rights: | http://hal.archives-ouvertes.fr/licences/copyright/ ; info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.7C50A67D |
| قاعدة البيانات: | BASE |
| DOI: | 10.1128/JVI.00403-20 |
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