PUBLICATION
Zebrafish spop promotes ubiquitination and degradation of mavs to suppress antiviral response via the lysosomal pathway
- Authors
- Yu, G.Q., Chen, M.J., Wang, Y.J., Liu, Y.Q., Zuo, M.Z., Zhang, Z.H., Li, G.X., Liu, B.Z., Li, M.
- ID
- ZDB-PUB-231130-20
- Date
- 2023
- Source
- International journal of biological macromolecules 256(Pt 2): 128451 (Journal)
- Registered Authors
- Yu, Guangqing
- Keywords
- Antiviral response, Innate immunity, Mavs, SVCV, Spop, Ubiquitination
- MeSH Terms
-
- Animals
- Antiviral Agents
- Immunity, Innate
- Signal Transduction*
- Ubiquitination
- Zebrafish*
- PubMed
- 38029910 Full text @ Int. J. Biol. Macromol.
Citation
Yu, G.Q., Chen, M.J., Wang, Y.J., Liu, Y.Q., Zuo, M.Z., Zhang, Z.H., Li, G.X., Liu, B.Z., Li, M. (2023) Zebrafish spop promotes ubiquitination and degradation of mavs to suppress antiviral response via the lysosomal pathway. International journal of biological macromolecules. 256(Pt 2):128451.
Abstract
Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) signaling pathways are required to be tightly controlled to initiate host innate immune responses. Fish mitochondrial antiviral signaling (mavs) is a key determinant in the RLR pathway, and its ubiquitination is associated with mavs activation. Here, we identified the zebrafish E3 ubiquitin ligase Speckle-type BTB-POZ protein (spop) negatively regulates mavs-mediated the type I interferon (IFN) responses. Consistently, overexpression of zebrafish spop repressed the activity of IFN promoter and reduced host ifn transcription, whereas knockdown spop by small interfering RNA (siRNA) transfection had the opposite effects. Accordingly, overexpression of spop dampened the cellular antiviral responses triggered by spring viremia of carp virus (SVCV). A functional domain assay revealed that the N-terminal substrate-binding MATH domain regions of spop were necessary for IFN suppression. Further assays indicated that spop interacts with mavs through the C-terminal transmembrane (TM) domain of mavs. Moreover, zebrafish spop selectively promotes K48-linked polyubiquitination and degradation of mavs through the lysosomal pathway to suppress IFN expression. Our findings unearth a post-translational mechanism by which mavs is regulated and reveal a role for spop in inhibiting antiviral innate responses.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping