PUBLICATION
Zebrafish RPZ5 Degrades the Phosphorylated IRF7 to Repress Interferon Production
- Authors
- Lu, L.F., Zhou, X.Y., Zhang, C., Li, Z.C., Chen, D.D., Liu, S.B., Li, S.
- ID
- ZDB-PUB-190816-5
- Date
- 2019
- Source
- Journal of virology 93(21): (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Antiviral Agents/immunology
- Antiviral Agents/metabolism
- Fish Diseases/immunology
- Fish Diseases/metabolism
- Fish Diseases/virology*
- Immunity, Innate/immunology*
- Interferon Regulatory Factors/genetics
- Interferon Regulatory Factors/metabolism
- Interferons/immunology
- Interferons/metabolism*
- Phosphorylation
- Rhabdoviridae/immunology*
- Rhabdoviridae Infections/immunology
- Rhabdoviridae Infections/metabolism
- Rhabdoviridae Infections/veterinary*
- Rhabdoviridae Infections/virology
- Ubiquitination
- Virus Replication
- Zebrafish/physiology
- Zebrafish/virology*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 31413136 Full text @ J. Virol.
Citation
Lu, L.F., Zhou, X.Y., Zhang, C., Li, Z.C., Chen, D.D., Liu, S.B., Li, S. (2019) Zebrafish RPZ5 Degrades the Phosphorylated IRF7 to Repress Interferon Production. Journal of virology. 93(21):.
Abstract
Interferon (IFN) production activated by phosphorylated interferon regulatory factor 7 (IRF7) is a pivotal process during host antiviral infection. For viruses, suppressing the host IFN response is beneficial for viral proliferation; in such cases, evoking host-derived IFN negative regulators would be very useful for viruses. Here, we report that the zebrafish rapunzel 5 (RPZ5) protein which activated by virus degraded phosphorylated IRF7 is activated by TBK1, leading to the reduction of IFN production. Upon viral infection, zebrafish rpz5 was significantly upregulated as ifn, in response to the stimulation. Overexpression of RPZ5 blunted the IFN expression induced by both viral and retinoic acid-inducible gene I (RIG-I) like-receptor (RLR) factors. Subsequently, RPZ5 interacted with RLRs but did not affect the stabilization of the proteins in the normal state. Interestingly, RPZ5 degraded the phosphorylated IRF7 under TBK1 activation through K48-linked ubiquitination. Finally, overexpression of RPZ5 remarkably reduced the host cell antiviral capacity. These findings suggest that zebrafish RPZ5 is a negative regulator of phosphorylated IRF7 and attenuates IFN expression during viral infection, providing insight into the IFN balance mechanism in fish.IMPORTANCE The phosphorylation of IRF7 is helpful for host IFN production to defend against viral infection, thus, it is a potential target for viruses to mitigate the antiviral response. We report that the fish RPZ5 is an IFN negative regulator induced by fish viruses and degrades the phosphorylated IRF7 activated by TBK1, leading to IFN suppression and promoting viral proliferation. These findings reveal a novel mechanism for interactions between the host cell and viruses in the lower vertebrate.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping