Aquatic birnavirus induces necrotic cell death via the mitochondria-mediated caspase pathway.
Aquatic birnavirus induces necrotic cell death by an ill-understood process. Presently, we demonstrate that infectious pancreatic necrosis virus (IPNV) induces post-apoptotic necrotic cell death through loss of mitochondrial membrane potential (MMP) followed by caspase-3 activation in CHSE-214 cells. Progressive phosphatidylserine externalization was observed at 6 h post-infection (p.i.). This was followed by the development of bulb-like vesicles (bleb formation) at 8 h p.i. Progressive loss of MMP was also observed in IPNV-infected CHSE-214 cells beginning at 6 h p.i. At 8 h and 12 h p.i., IPNV-infected cells demonstrated a dramatic increase in MMP loss, rapid entry into necrotic cell death, and activation of caspase-9 and -3. Additionally, treatment with an inhibitor of MMP loss, bongkrekic acid, an adenine nucleotide translocase inhibitor, blocked IPNV-induced PS exposure and MMP loss, as well as reduced the activation of caspase-3. Taken together, our results suggest that IPNV induces apoptotic cell death via loss of MMP, thereby triggering secondary necrosis and caspases-3 activation. Furthermore, this death-signaling pathway is disrupted by bongkrekic acid in fish cells, indicating that this drug may serve to modulate IPNV-induced pathogenesis.
Chen
Po-Chun
PC
Laboratory of Molecular Virology and Biotechnology, Institute of Biotechnology, National Cheng Kung University, Tainan 701, Taiwan.
Wu
Jen-Leih
JL
Her
Guor Mour
GM
Hong
Jiann-Ruey
JR
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D018059:Birnaviridae / Q000276:immunology*; D018175:Birnaviridae Infections / Q000276:immunology / Q000662:veterinary*; D001865:Bongkrekic Acid / Q000494:pharmacology; D020169:Caspases / Q000276:immunology*; D016923:Cell Death / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D008928:Mitochondria / Q000201:enzymology*; D010718:Phosphatidylserines / Q000494:pharmacology; D012474:Salmon
D000900:Anti-Bacterial Agents; D010718:Phosphatidylserines; D001865:Bongkrekic Acid; D020169:Caspases