Tick-borne flavivirus NS5 antagonizes interferon signaling by inhibiting the catalytic activity of TYK2.
JAK-STAT signaling
TYK2
emerging viruses
interferon evasion by viruses
tick-borne flaviviruses
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
06 Dec 2023
06 Dec 2023
Historique:
revised:
04
10
2023
received:
02
05
2023
accepted:
06
10
2023
pmc-release:
20
10
2024
medline:
11
12
2023
pubmed:
20
10
2023
entrez:
20
10
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37860832
doi: 10.15252/embr.202357424
pmc: PMC10702846
doi:
Substances chimiques
TYK2 Kinase
EC 2.7.10.2
Viral Nonstructural Proteins
0
Interferons
9008-11-1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e57424Subventions
Organisme : Agence Nationale de la Recherche (ANR)
ID : ANR-19-CE35-0015
Organisme : Agence Nationale de la Recherche (ANR)
ID : ANR-20-CE11-0024
Informations de copyright
© 2023 The Authors.
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