Zebrafish ISG15 Exerts a Strong Antiviral Activity against RNA and DNA Viruses and Regulates the Interferon Response
| Autor: | L.M. van der Aa, Armel Houel, Christelle Langevin, Aurélie Lunazzi, Abdallah Harmache, Michel Brémont, Valérie Briolat, Pierre Boudinot, Corinne Torhy, Jean-Pierre Levraud |
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| Přispěvatelé: | Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut National de la Recherche Agronomique (INRA), Cell Biology and Immunology Group [Wageningen] (CBI), Department of Animal Sciences [Wageningen], Wageningen University and Research [Wageningen] (WUR)-Wageningen University and Research [Wageningen] (WUR), Macrophages et Développement de l'Immunité, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), This work was supported by the Institut National de la Recherche Agronomique, by Wageningen University, and by the Institut Pasteur. It was partly funded by the ANR grant Zebraflam (ANR-10-MIDI-009)., We thank N. Palmic for excellent technical help with zebrafish infections., ANR-10-MIDI-0009,ZebraFlam,Signaux et cellules de la réponse inflammatoire: suivi en temps réel chez un vertébré entier, le danio zébré(2010), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2013 |
| Předmět: |
molecular cloning
MESH: Sequence Analysis DNA brachydanio rerio Cellular Response to Infection [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity mycobacterial disease Interferon MESH: Animals ifn gamma immunity Zebrafish virus à arn 0303 health sciences Novirhabdovirus induced 15 kda protein biology RIG-I MESH: RNA Viruses / immunology activité antivirale 030302 biochemistry & molecular biology 3. Good health infected-cells Viperin MESH: Ubiquitin / genetics stimulated gene isg15 Protein Binding medicine.drug MESH: Zebrafish / immunology Molecular Sequence Data ifn-gamma immunity Immunology ubiquitin-like protein Celbiologie en Immunologie i interferon Microbiology MESH: Ubiquitin / immunology Cell Line MESH: Viral Proteins / metabolism MESH: Zebrafish / genetics virus à adn Viral Proteins 03 medical and health sciences ubiquitin like protein MESH: Interferons / immunology rig i Virology medicine Animals RNA Viruses MESH: Protein Binding expression analysis Gene 030304 developmental biology MESH: Molecular Sequence Data Ubiquitin molecular-cloning rig-i DNA Viruses RNA Sequence Analysis DNA interféron infected cells induced 15-kda protein biology.organism_classification ISG15 MESH: Cell Line MESH: Interferons / biosynthesis Cell Biology and Immunology MESH: Zebrafish / virology MESH: Protein Processing Post-Translational Insect Science MESH: DNA Viruses / immunology WIAS Interferons Protein Processing Post-Translational |
| Zdroj: | Journal of Virology 18 (87), 10025-10036. (2013) Journal of Virology Journal of Virology 87 (2013) 18 Journal of Virology, 87(18), 10025-10036 Journal of Virology, American Society for Microbiology, 2013, 87 (18), pp.10025-10036. ⟨10.1128/JVI.01294-12⟩ Journal of Virology, 2013, 87 (18), pp.10025-10036. ⟨10.1128/JVI.01294-12⟩ |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.01294-12 |
| Popis: | ISG15, a 15-kDa interferon-induced protein that participates in antiviral defenses of mammals, is highly conserved among vertebrates. In fish, as in mammals, viral infection and interferon treatment induce isg15 expression. The two ubiquitin-like domains of ISG15 and the presence of a consensus LRLRGG sequence in the C-terminal region, which is required for the covalent conjugation to a substrate protein, are also conserved in fish. Our data demonstrate that overexpression of zebrafish ISG15 (zf-ISG15) in EPC cells is sufficient to inhibit viral infection by RNA viruses belonging to the genera Novirhabdovirus and Birnavirus and by DNA viruses of the genus Iridovirus . In coexpression experiments with IHNV proteins, we demonstrate specific ISGylation of phosphoprotein and nonvirion protein. Mutation of the glycine residues in the consensus LRLRGG motif abolishes zf-ISG15 conjugation to these proteins and the cellular protection against viral infection, thus connecting ISGylation and ISG15-dependent viral restriction. Additionally, zf-ISG15 overexpression triggers induction of the rig-I and viperin genes as well as, to a lesser extent, the IFN gene. Overall, our data demonstrate the antiviral effect of a fish ISG15 protein, revealing the conservation among vertebrates of an ISGylation mechanism likely directed against viruses. Furthermore, our findings indicate that zf-ISG15 affects the IFN system at several levels, and its study shall shed further light on the evolution of the complex regulation of the innate antiviral response in vertebrate cells. |
| Databáze: | OpenAIRE |
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