PUBLICATION
Zebrafish phd3 Negatively Regulates Antiviral Responses via Suppression of Irf7 Transactivity Independent of Its Prolyl Hydroxylase Activity
- Authors
- Yu, G., Li, X., Zhou, Z., Tang, J., Wang, J., Liu, X., Fan, S., Ouyang, G., Xiao, W.
- ID
- ZDB-PUB-200717-3
- Date
- 2020
- Source
- Journal of immunology (Baltimore, Md. : 1950) 205(4): 1135-1146 (Journal)
- Registered Authors
- Xiao, Wuhan, Yu, Guangqing
- Keywords
- none
- MeSH Terms
-
- Animals
- Antiviral Agents/pharmacology
- Cell Line
- HEK293 Cells
- Humans
- Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
- Hypoxia-Inducible Factor-Proline Dioxygenases/metabolism*
- Interferon Regulatory Factors/metabolism*
- Signal Transduction/physiology
- Ubiquitination/physiology
- Virus Diseases/drug therapy
- Virus Diseases/metabolism*
- Viruses/drug effects
- Zebrafish/metabolism*
- Zebrafish Proteins/metabolism*
- PubMed
- 32669312 Full text @ J. Immunol.
Citation
Yu, G., Li, X., Zhou, Z., Tang, J., Wang, J., Liu, X., Fan, S., Ouyang, G., Xiao, W. (2020) Zebrafish phd3 Negatively Regulates Antiviral Responses via Suppression of Irf7 Transactivity Independent of Its Prolyl Hydroxylase Activity. Journal of immunology (Baltimore, Md. : 1950). 205(4):1135-1146.
Abstract
Prolyl hydroxylase domain (PHD)-containing enzyme 3 belongs to the Caenorhabditis elegans gene egl-9 family of prolyl hydroxylases, which has initially been revealed to hydroxylate hypoxia-inducible factor α (HIF-α) and mediate HIF-α degradation. In addition to modulating its target function by hydroxylation, PHD3 has been also shown to influence its binding partners' function independent of its prolyl hydroxylase activity. In this study, we report that overexpression of zebrafish phd3 suppresses cellular antiviral response. Moreover, disruption of phd3 in zebrafish increases the survival rate upon spring viremia of carp virus exposure. Further assays indicate that phd3 interacts with irf7 through the C-terminal IRF association domain of irf7 and diminishes K63-linked ubiquitination of irf7. However, the enzymatic activity of phd3 is not required for phd3 to inhibit irf7 transactivity. This study provides novel insights into phd3 function and sheds new light on the regulation of irf7 in retinoic acid-inducible gene I-like receptor signaling.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping