Tick-borne encephalitis virus NS4A ubiquitination antagonizes type I interferon-stimulated STAT1/2 signalling pathway.
Cell Line
DEAD Box Protein 58
/ metabolism
Encephalitis Viruses, Tick-Borne
/ metabolism
Humans
Interferon Regulatory Factors
/ antagonists & inhibitors
Interferon Type I
/ antagonists & inhibitors
Interferon-Induced Helicase, IFIH1
/ metabolism
Interferon-Stimulated Gene Factor 3, gamma Subunit
/ metabolism
Interferon-beta
/ genetics
Lysine
/ metabolism
Phosphorylation
Protein Interaction Domains and Motifs
Protein Multimerization
Receptors, Immunologic
STAT1 Transcription Factor
/ metabolism
STAT2 Transcription Factor
/ metabolism
Signal Transduction
Ubiquitination
Up-Regulation
Viral Nonstructural Proteins
/ metabolism
src Homology Domains
NS4A
STAT1
STAT2
Tick-borne encephalitis virus (TBEV)
ubiquitination
Journal
Emerging microbes & infections
ISSN: 2222-1751
Titre abrégé: Emerg Microbes Infect
Pays: United States
ID NLM: 101594885
Informations de publication
Date de publication:
Dec 2020
Dec 2020
Historique:
pubmed:
21
3
2020
medline:
9
4
2020
entrez:
21
3
2020
Statut:
ppublish
Résumé
Tick-borne encephalitis virus (TBEV) accounts for approximately 10,000 annual cases of severe encephalitis in Europe and Asia and causes encephalitis in humans. In this study, we demonstrate TBEV appears to activate the interferon (IFN)-β dependent on RIG-I/MDA5. Both the IFN-β accumulation and the IFN stimulated genes (ISGs) transcription greatly delay. Further studies reveal that TBEV NS4A could block the phosphorylation and dimerization of STAT1/STAT2 to affect type I and II IFN-mediated STAT signalling. Additional data indicate that the residue at K132 of TBEV NS4A could be modified by ubiquitination and this modification is necessary for the interaction of NS4A with STAT1. Dynamic ubiquitination of the NS4 protein during TBEV infection might account for delayed activation of the ISGs. These results define the TBEV NS4A as an antagonist of the IFN response, by demonstrating a correlation between the association and STAT interference. Our findings provide a foundation for further understanding how TBEV evade innate immunity and a potential viral target for intervention.
Identifiants
pubmed: 32196427
doi: 10.1080/22221751.2020.1745094
pmc: PMC7170394
doi:
Substances chimiques
IRF9 protein, human
0
Interferon Regulatory Factors
0
Interferon Type I
0
Interferon-Stimulated Gene Factor 3, gamma Subunit
0
NS4A protein, flavivirus
0
Receptors, Immunologic
0
STAT1 Transcription Factor
0
STAT1 protein, human
0
STAT2 Transcription Factor
0
STAT2 protein, human
0
Viral Nonstructural Proteins
0
Interferon-beta
77238-31-4
RIGI protein, human
EC 3.6.1.-
IFIH1 protein, human
EC 3.6.1.-
DEAD Box Protein 58
EC 3.6.4.13
Interferon-Induced Helicase, IFIH1
EC 3.6.4.13
Lysine
K3Z4F929H6
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
714-726Références
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