PUBLICATION
Dual modifying of MAVS at lysine 7 by SIRT3-catalyzed deacetylation and SIRT5-catalyzed desuccinylation orchestrates antiviral innate immunity
- Authors
- Liu, X., Zhu, C., Jia, S., Deng, H., Tang, J., Sun, X., Zeng, X., Chen, X., Wang, Z., Liu, W., Liao, Q., Zha, H., Cai, X., Xiao, W.
- ID
- ZDB-PUB-240419-3
- Date
- 2024
- Source
- Proceedings of the National Academy of Sciences of the United States of America 121: e2314201121e2314201121 (Journal)
- Registered Authors
- Xiao, Wuhan
- Keywords
- MAVS, SIRT3, SIRT5, deacetylation, desuccinylation
- MeSH Terms
-
- Adaptor Proteins, Signal Transducing/genetics
- Animals
- Immunity, Innate
- Lysine
- Mice
- Sirtuin 3*/genetics
- Sirtuins*/genetics
- Virus Diseases*
- Zebrafish
- Zebrafish Proteins
- PubMed
- 38635631 Full text @ Proc. Natl. Acad. Sci. USA
Citation
Liu, X., Zhu, C., Jia, S., Deng, H., Tang, J., Sun, X., Zeng, X., Chen, X., Wang, Z., Liu, W., Liao, Q., Zha, H., Cai, X., Xiao, W. (2024) Dual modifying of MAVS at lysine 7 by SIRT3-catalyzed deacetylation and SIRT5-catalyzed desuccinylation orchestrates antiviral innate immunity. Proceedings of the National Academy of Sciences of the United States of America. 121:e2314201121e2314201121.
Abstract
To effectively protect the host from viral infection while avoiding excessive immunopathology, the innate immune response must be tightly controlled. However, the precise regulation of antiviral innate immunity and the underlying mechanisms remain unclear. Here, we find that sirtuin3 (SIRT3) interacts with mitochondrial antiviral signaling protein (MAVS) to catalyze MAVS deacetylation at lysine residue 7 (K7), which promotes MAVS aggregation, as well as TANK-binding kinase I and IRF3 phosphorylation, resulting in increased MAVS activation and enhanced type I interferon signaling. Consistent with these findings, loss of Sirt3 in mice and zebrafish renders them more susceptible to viral infection compared to their wild-type (WT) siblings. However, Sirt3 and Sirt5 double-deficient mice exhibit the same viral susceptibility as their WT littermates, suggesting that loss of Sirt5 in Sirt3-deficient mice may counteract the increased viral susceptibility displayed in Sirt3-deficient mice. Thus, we not only demonstrate that SIRT3 positively regulates antiviral immunity in vitro and in vivo, likely via MAVS, but also uncover a previously unrecognized mechanism by which SIRT3 acts as an accelerator and SIRT5 as a brake to orchestrate antiviral innate immunity.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping