Tick-borne flavivirus NS5 antagonizes interferon signaling by inhibiting the catalytic activity of TYK2.

Autor: Gracias S; Virus Sensing and Signaling Unit, CNRS UMR3569, Institut Pasteur, Université de Paris Cité, Paris, France., Chazal M; Virus Sensing and Signaling Unit, CNRS UMR3569, Institut Pasteur, Université de Paris Cité, Paris, France., Decombe A; AFMB UMR 7257, CNRS, Aix Marseille Université, Marseille, France., Unterfinger Y; UMR1161 Virologie Laboratoire de Santé Animale, Anses, INRAE, Ecole Nationale Vétérinaire d'Alfort, Université Paris-Est, Maisons-Alfort, France., Sogues A; Structural and Molecular Microbiology, VIB-VUB, Center for Structural Biology, Brussels, Belgium., Pruvost L; Virus Sensing and Signaling Unit, CNRS UMR3569, Institut Pasteur, Université de Paris Cité, Paris, France., Robert V; AFMB UMR 7257, CNRS, Aix Marseille Université, Marseille, France., Lacour SA; UMR1161 Virologie Laboratoire de Santé Animale, Anses, INRAE, Ecole Nationale Vétérinaire d'Alfort, Université Paris-Est, Maisons-Alfort, France., Lemasson M; UMR1161 Virologie Laboratoire de Santé Animale, Anses, INRAE, Ecole Nationale Vétérinaire d'Alfort, Université Paris-Est, Maisons-Alfort, France.; Phagos Pépinière Genopole Entreprise, Evry-Courcouronnes, France., Sourisseau M; UMR1161 Virologie Laboratoire de Santé Animale, Anses, INRAE, Ecole Nationale Vétérinaire d'Alfort, Université Paris-Est, Maisons-Alfort, France., Li Z; Unit of Cytokine Signaling, INSERM U122, Institut Pasteur, Paris, France.; Human Evolutionary Genetics Unit, CNRS UMR2000, Institut Pasteur, Université de Paris Cité, Paris, France., Richardson J; UMR1161 Virologie Laboratoire de Santé Animale, Anses, INRAE, Ecole Nationale Vétérinaire d'Alfort, Université Paris-Est, Maisons-Alfort, France., Pellegrini S; Unit of Cytokine Signaling, INSERM U122, Institut Pasteur, Paris, France., Decroly E; AFMB UMR 7257, CNRS, Aix Marseille Université, Marseille, France., Caval V; Virus Sensing and Signaling Unit, CNRS UMR3569, Institut Pasteur, Université de Paris Cité, Paris, France., Jouvenet N; Virus Sensing and Signaling Unit, CNRS UMR3569, Institut Pasteur, Université de Paris Cité, Paris, France.
Jazyk: angličtina
Zdroj: EMBO reports [EMBO Rep] 2023 Dec 06; Vol. 24 (12), pp. e57424. Date of Electronic Publication: 2023 Oct 20.
DOI: 10.15252/embr.202357424
Abstrakt: The mechanisms utilized by different flaviviruses to evade antiviral functions of interferons are varied and incompletely understood. Using virological approaches, biochemical assays, and mass spectrometry analyses, we report here that the NS5 protein of tick-borne encephalitis virus (TBEV) and Louping Ill virus (LIV), two related tick-borne flaviviruses, antagonize JAK-STAT signaling through interactions with the tyrosine kinase 2 (TYK2). Co-immunoprecipitation (co-IP) experiments, yeast gap-repair assays, computational protein-protein docking and functional studies identify a stretch of 10 residues of the RNA dependent RNA polymerase domain of tick-borne flavivirus NS5, but not mosquito-borne NS5, that is critical for interactions with the TYK2 kinase domain. Additional co-IP assays performed with several TYK2 orthologs reveal that the interaction is conserved across mammalian species. In vitro kinase assays show that TBEV and LIV NS5 reduce the catalytic activity of TYK2. Our results thus illustrate a novel mechanism by which viruses suppress the interferon response.
(© 2023 The Authors.)
Databáze: MEDLINE
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