Zika virus alters centrosome organization to suppress the innate immune response.
Zika virus
centrosome
innate immunity
microcephaly
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
05 09 2022
05 09 2022
Historique:
revised:
31
05
2022
received:
03
12
2020
accepted:
15
06
2022
pubmed:
7
7
2022
medline:
9
9
2022
entrez:
6
7
2022
Statut:
ppublish
Résumé
Zika virus (ZIKV) is a flavivirus transmitted via mosquitoes and sex to cause congenital neurodevelopmental defects, including microcephaly. Inherited forms of microcephaly (MCPH) are associated with disrupted centrosome organization. Similarly, we found that ZIKV infection disrupted centrosome organization. ZIKV infection disrupted the organization of centrosomal proteins including CEP63, a MCPH-associated protein. The ZIKV nonstructural protein NS3 bound CEP63, and expression of NS3 was sufficient to alter centrosome architecture and CEP63 localization. Loss of CEP63 suppressed ZIKV-induced centrosome disorganization, indicating that ZIKV requires CEP63 to disrupt centrosome organization. ZIKV infection or CEP63 loss decreased the centrosomal localization and stability of TANK-binding kinase 1 (TBK1), a regulator of the innate immune response. ZIKV infection also increased the centrosomal accumulation of the CEP63 interactor DTX4, a ubiquitin ligase that degrades TBK1. Therefore, we propose that ZIKV disrupts CEP63 function to increase centrosomal DTX4 localization and destabilization of TBK1, thereby tempering the innate immune response.
Identifiants
pubmed: 35793002
doi: 10.15252/embr.202052211
pmc: PMC9442309
doi:
Substances chimiques
CEP63 protein, human
0
Cell Cycle Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e52211Subventions
Organisme : NIAID NIH HHS
ID : T32 AI060537
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM141323
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH114825
Pays : United States
Organisme : NINDS NIH HHS
ID : R35 NS097305
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE029454
Pays : United States
Organisme : NINDS NIH HHS
ID : F31 NS108615
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR054396
Pays : United States
Organisme : NINDS NIH HHS
ID : R21 NS104633
Pays : United States
Informations de copyright
© 2022 The Authors.
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