PUBLICATION
Aquatic birnavirus capsid protein, VP3, induces apoptosis via the Bad-mediated mitochondria pathway in fish and mouse cells
- Authors
- Chiu, C.L., Wu, J.L., Her, G.M., Chou, Y.L., and Hong, J.R.
- ID
- ZDB-PUB-100211-14
- Date
- 2010
- Source
- Apoptosis : an international journal on programmed cell death 15(6): 653-668 (Journal)
- Registered Authors
- Her, Guor Muor, Hong, Jiann-Ruey, Wu, Jen-Leih
- Keywords
- Infectious pancreatic necrosis virus, Submajor capsid VP3, Pro-apoptotic Bad, Mitochondrial membrane potential loss, zfBcl-xL, Antisense RNA
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Apoptosis*
- Base Sequence
- Birnaviridae Infections/metabolism
- Birnaviridae Infections/physiopathology
- Birnaviridae Infections/veterinary*
- Birnaviridae Infections/virology
- Capsid Proteins/genetics
- Capsid Proteins/metabolism*
- Caspase 3/metabolism
- Caspase 9/metabolism
- Cell Line
- Fish Diseases/genetics
- Fish Diseases/metabolism
- Fish Diseases/physiopathology*
- Fish Diseases/virology
- Fish Proteins/genetics
- Fish Proteins/metabolism*
- Fishes
- Gene Expression Regulation, Viral
- Infectious pancreatic necrosis virus/genetics
- Infectious pancreatic necrosis virus/metabolism*
- Mice
- Mitochondria/metabolism*
- Molecular Sequence Data
- NIH 3T3 Cells
- Signal Transduction*
- Up-Regulation
- bcl-Associated Death Protein/genetics
- bcl-Associated Death Protein/metabolism*
- PubMed
- 20131002 Full text @ Apoptosis
Citation
Chiu, C.L., Wu, J.L., Her, G.M., Chou, Y.L., and Hong, J.R. (2010) Aquatic birnavirus capsid protein, VP3, induces apoptosis via the Bad-mediated mitochondria pathway in fish and mouse cells. Apoptosis : an international journal on programmed cell death. 15(6):653-668.
Abstract
Aquatic birnavirus induces post-apoptotic necrotic cell death via a newly synthesized protein-dependent pathway. However, the involvement of viral genome-encoded protein(s) in this death process remains unknown. In the present study, we demonstrated that the submajor capsid protein, VP3, up-regulates the pro-apoptotic protein, Bad, in fish and mouse cells. Western blot analysis revealed that VP3 was expressed in CHSE-214 cells at 4 h post-infection (pi), indicating an early role during viral replication. We cloned the VP3 gene and tested its function in fish and mouse cells; VP3 overexpression induced apoptotic cell death by TUNEL assay. In addition, it up-regulated Bad gene expression in zebrafish ZLE cells by threefold at 12 h post-transfection (pt) and in mouse NIH3T3 cells by tenfold at 24 h pt. VP3 up-regulation of Bad expression altered mitochondria function, inducing mitochondrial membrane potential (MMP) loss and activating initiator caspase-9 and effector caspase-3. Furthermore, reduced Bad expression (65% reduction), MMP loss (up to 40%), and enhanced cell viability (up to 60%) upon expression of VP3 antisense RNA in CHSE-214 cells at 24 h post-IPNV infection was observed. Finally, overexpression of the anti-apoptotic gene, zfBcl-xL, reduced VP3-induced apoptotic cell death and caspase-3 activation at 24 h in fish cells. Taken together, these results suggest that aquatic birnavirus VP3 induces apoptosis via up-regulation of Bad expression and mitochondrial disruption, which activates a downstream caspase-3-mediated death pathway that is blocked by zfBcl-xL.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping