ZC3HAV1 facilitates STING activation and enhances inflammation.
Animals
Inflammation
/ metabolism
Mice
Membrane Proteins
/ metabolism
Humans
Signal Transduction
Herpesvirus 1, Human
/ physiology
Mice, Inbred C57BL
Interferon Regulatory Factor-3
/ metabolism
HEK293 Cells
Mice, Knockout
Herpes Simplex
/ virology
Endoplasmic Reticulum
/ metabolism
NF-kappa B
/ metabolism
Golgi Apparatus
/ metabolism
Immunity, Innate
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
30 Oct 2024
30 Oct 2024
Historique:
received:
17
03
2024
accepted:
21
10
2024
medline:
31
10
2024
pubmed:
31
10
2024
entrez:
31
10
2024
Statut:
epublish
Résumé
Stimulator of interferon genes (STING) is vital in the cytosolic DNA-sensing process and critical for initiating the innate immune response, which has important functions in host defense and contributes to the pathogenesis of inflammatory diseases. Zinc finger CCCH-type antiviral protein 1 (ZC3HAV1) specifically binds the CpG dinucleotides in the viral RNAs of multiple viruses and promotes their degradation. ZAPS (ZC3HAV1 short isoform) is a potent stimulator of retinoid acid-inducible gene I (RIG-I) signaling during the antiviral response. However, how ZC3HAV1 controls STING signaling is unclear. Here, we show that ZC3HAV1 specifically potentiates STING activation by associating with STING to promote its oligomerization and translocation from the endoplasmic reticulum (ER) to the Golgi, which facilitates activation of IRF3 and NF-κB pathway. Accordingly, Zc3hav1 deficiency protects mice against herpes simplex virus-1 (HSV-1) infection- or 5,6-dimethylxanthenone-4-acetic acid (DMXAA)-induced inflammation in a STING-dependent manner. These results indicate that ZC3HAV1 is a key regulator of STING signaling, which suggests its possible use as a therapeutic target for STING-dependent inflammation.
Identifiants
pubmed: 39478149
doi: 10.1038/s42003-024-07116-2
pii: 10.1038/s42003-024-07116-2
doi:
Substances chimiques
Membrane Proteins
0
Sting1 protein, mouse
0
STING1 protein, human
0
Interferon Regulatory Factor-3
0
NF-kappa B
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1418Subventions
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 82172276
Organisme : Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation)
ID : ZR2023LZL007
Organisme : Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation)
ID : ZR2022QH032
Organisme : Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation)
ID : ZR2020MH087
Informations de copyright
© 2024. The Author(s).
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