title: Aquatic birnavirus infection activates the transcription factor NF-kappaB via tyrosine kinase signalling leading to cell death.
abstract: Our previous studies found that infectious pancreatic necrosis virus (IPNV) induces host apoptotic cell death, possibly through a newly synthesized protein trigger. Here, we examine whether IPNV infection can induce NF-kappaB activation through tyrosine kinase signalling of CHSE-214 cell death (host cell death). Using the electrophoretic mobility shift assay (EMSA) to detect transcription factor activation, we found that NF-kappaB is apparently activated 6-8 h post-IPNV infection. Using genistein (100 microg mL(-1); a tyrosine kinase inhibitor) to determine whether NF-kappaB activation requires tyrosine kinase activation, we found genistein blocks NF-kappaB activation at 8 h post-infection (p.i), and either enhances cell viability up to 50% at 12 h p.i. or blocks DNA fragmentation at 24 h p.i. Furthermore, the proteasome inhibitors PSI-I and PSI-II (both at 40 microm) also effectively blocked the NF-kappaB activation as well as stimulating a 30% increase in cell viability (30% decrease in apoptosis) at 8 and 12 h p.i. Taken together our data suggest that IPNV may induce NF-kappaB activation through tyrosine kinase signalling, which may be associated with induction of apoptosis.
authors.affiliation: Laboratory of Molecular Virology and Biotechnology, Institute of Biotechnology, National Cheng-Kung University, Tainan, Taiwan.
authors.forename: J-R
authors.initials: JR
authors.lastname: Hong
authors.forename: B-J
authors.initials: BJ
authors.lastname: Guan
authors.forename: G M
authors.initials: GM
authors.lastname: Her
authors.forename: O
authors.initials: O
authors.lastname: Evensen
authors.forename: N
authors.initials: N
authors.lastname: Santi
authors.forename: J-L
authors.initials: JL
authors.lastname: Wu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018059:Birnaviridae / Q000502:physiology*; D018175:Birnaviridae Infections / Q000201:enzymology / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D016923:Cell Death; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D005393:Fish Diseases / Q000201:enzymology / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D019833:Genistein / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012474:Salmon / Q000378:metabolism / Q000821:virology*; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D015853:Cysteine Proteinase Inhibitors; D016328:NF-kappa B; D009842:Oligopeptides; D047428:Protein Kinase Inhibitors; C090535:benzyloxycarbonyl-isoleucyl-glutamyl(O-tert-butyl)-alanyl-leucinal; D019833:Genistein; D011505:Protein-Tyrosine Kinases