PUBLICATION
Opposing effects of deubiquitinase OTUD3 in innate immunity against RNA and DNA viruses
- Authors
- Cai, X., Zhou, Z., Zhu, J., Liu, X., Ouyang, G., Wang, J., Li, Z., Li, X., Zha, H., Zhu, C., Rong, F., Tang, J., Liao, Q., Chen, X., Xiao, W.
- ID
- ZDB-PUB-220609-5
- Date
- 2022
- Source
- Cell Reports 39: 110920 (Journal)
- Registered Authors
- Li, Zhi, Ouyang, Gang, Rong, Fangjing, Xiao, Wuhan
- Keywords
- CP: Immunology, CP: Molecular biology, MDA5, OTUD3, RIG-I, cGAS, deubiquitination, innate immunity
- MeSH Terms
-
- Animals
- Antiviral Agents
- DEAD Box Protein 58/metabolism
- DNA Viruses
- Deubiquitinating Enzymes
- Immunity, Innate
- Interferon-Induced Helicase, IFIH1/metabolism
- Mice
- Nucleotidyltransferases
- RNA Viruses*
- RNA, Viral/metabolism
- Zebrafish*/metabolism
- PubMed
- 35675783 Full text @ Cell Rep.
Citation
Cai, X., Zhou, Z., Zhu, J., Liu, X., Ouyang, G., Wang, J., Li, Z., Li, X., Zha, H., Zhu, C., Rong, F., Tang, J., Liao, Q., Chen, X., Xiao, W. (2022) Opposing effects of deubiquitinase OTUD3 in innate immunity against RNA and DNA viruses. Cell Reports. 39:110920.
Abstract
Retinoic acid-inducible-I (RIG-I), melanoma differentiation-associated gene 5 (MDA5), and cyclic GMP-AMP synthase (cGAS) genes encode essential cytosolic receptors mediating antiviral immunity against viruses. Here, we show that OTUD3 has opposing role in response to RNA and DNA virus infection by removing distinct types of RIG-I/MDA5 and cGAS polyubiquitination. OTUD3 binds to RIG-I and MDA5 and removes K63-linked ubiquitination. This serves to reduce the binding of RIG-I and MDA5 to viral RNA and the downstream adaptor MAVS, leading to the suppression of the RNA virus-triggered innate antiviral responses. Meanwhile, OTUD3 associates with cGAS and targets at Lys279 to deubiquitinate K48-linked ubiquitination, resulting in the enhancement of cGAS protein stability and DNA-binding ability. As a result, Otud3-deficient mice and zebrafish are more resistant to RNA virus infection but are more susceptible to DNA virus infection. These findings demonstrate that OTUD3 limits RNA virus-triggered innate immunity but promotes DNA virus-triggered innate immunity.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping