PUBLICATION
TBK1 Isoform Inhibits Grass Carp Reovirus Infection by Targeting the Degradation of Viral Nonstructural Proteins NS80 and NS38
- Authors
- Zhang, J., Chang, M.X.
- ID
- ZDB-PUB-221130-4
- Date
- 2022
- Source
- Journal of immunology (Baltimore, Md. : 1950) 210(2): 191-203 (Journal)
- Registered Authors
- Chang, Mingxian
- Keywords
- none
- MeSH Terms
-
- Animals
- Antibodies, Viral/metabolism
- Carps*/metabolism
- Cell Line
- Fish Diseases*
- Protein Isoforms/metabolism
- Reoviridae*
- Reoviridae Infections*/veterinary
- Viral Nonstructural Proteins/metabolism
- Zebrafish
- PubMed
- 36445692 Full text @ J. Immunol.
Citation
Zhang, J., Chang, M.X. (2022) TBK1 Isoform Inhibits Grass Carp Reovirus Infection by Targeting the Degradation of Viral Nonstructural Proteins NS80 and NS38. Journal of immunology (Baltimore, Md. : 1950). 210(2):191-203.
Abstract
TANK-binding kinase 1 (TBK1) undergoes alternative splicing, and the previously reported TBK1 isoforms are negative regulators of RIG-I-like receptor-mediated type I IFN production. Although a study has suggested that grass carp TBK1 has an opposite effect at high- and low-titer of grass carp reovirus (GCRV) infection, the functions of grass carp TBK1 isoforms in GCRV infection remain unclear. In this study, we show that a TBK1 isoform from grass carp (Ctenopharyngodon idellus) named as gcTBK1_tv3, which has a 1-aa difference with zebrafish TBK1_tv3, inhibits the replication and infection of GCRV both at high and low titers of infection in C. idellus kidney cells. gcTBK1_tv3 can colocalize and interact with the NS80 and NS38 proteins of GCRV. Furthermore, gcTBK1_tv3 specifically degrades the NS80 and NS38 proteins of GCRV through the ubiquitin-proteasome pathway. Mechanistically, gcTBK1_tv3 promotes the degradation of NS80 or NS38 for K48-linked ubiquitination by targeting the Lys503 residue of NS80 or Lys328 residue of NS38, respectively, which ultimately impairs the production of cytoplasmic viral inclusion bodies and limits GCRV replication and infection. Taken together, our findings provide insight into the function of TBK1 isoform in the antiviral immune response and demonstrate that TBK1 isoform can target the nonstructural proteins of GCRV for impairing the formation of viral inclusion bodies.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping