Zika virus NS2A inhibits interferon signaling by degradation of STAT1 and STAT2.
Ifn evasion
Ifn signaling
Ns2a
Zika virus
degradation
interferon
phosphorylation
stat1
stat2
Journal
Virulence
ISSN: 2150-5608
Titre abrégé: Virulence
Pays: United States
ID NLM: 101531386
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
entrez:
2
8
2021
pubmed:
3
8
2021
medline:
28
1
2022
Statut:
ppublish
Résumé
The Interferon (IFN) response is crucial to restrain pathogenic infections. Investigations into flavivirus-host interactions reported that the high virulence is linked to innate immune evasion. Zika Virus (ZIKV) has developed diversified strategies to evade the innate immune system. We report that the viral protein NS2A counteracts the IFN response by strongly suppressing the IFN signaling. NS2A targets transcription factors STAT1 and STAT2, to impede their nuclear localization, thereby suppressing the transcription of ISRE promoter and IFN-stimulated genes. We found that NS2A promotes degradation of STAT1 and STAT2. Treatment of NS2A transfected cells with MG132 restores the levels of both transcription factors, suggesting the involvement of the proteasome system. Given the impact that the IFN antagonism has on flavivirus virulence, the knowledge gained by characterizing the mechanism through which ZIKV evades the IFN response paves the ground for new strategies to attenuate the pathogenesis and to develop countermeasures against effective pharmacological targets.
Identifiants
pubmed: 34338586
doi: 10.1080/21505594.2021.1935613
pmc: PMC8331042
doi:
Substances chimiques
STAT1 Transcription Factor
0
STAT1 protein, human
0
STAT2 Transcription Factor
0
STAT2 protein, human
0
Viral Nonstructural Proteins
0
Interferons
9008-11-1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1580-1596Références
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