title: Giant seaperch iridovirus infection upregulates Bas and Bak expression, leading to apoptotic death of fish cells.
abstract: The giant seaperch iridovirus (GSIV) induces host cell apoptosis by a poorly-understood process. In this study, GSIV is shown to upregulate the pro-apoptotic death genes Bax and Bak at the middle replication stage, and factors in the grouper fin cell line (GF-1) are shown to modulate this process. Studying the mechanism of cell death, we found that upregulated, de novo-synthesized Bax and Bak proteins formed heterodimers. This up-regulation process correlated with mitochondrial membrane potential (MMP) loss, increased caspase-3 activity, and increased apoptotic cell death. All effects were diminished by treatment of infected GF-1 cells with the protein synthesis inhibitor cycloheximide. Interestingly, overexpression of the anti-apoptotic gene Bcl-xL also diminished GSIV-induced mitochondria-mediated cell death, increasing host cell viability and decreasing MMP loss at the early replication stage. Our data suggest that GSIV induces GF-1 apoptotic cell death through up-regulation of the pro-apoptotic genes Bax and Bak, which are regulated by Bcl-xL overexpression on mitochondria in GF-1 cells.
authors.affiliation: Laboratory of Molecular Virology and Biotechnology, Institute of Biotechnology, National Cheng-Kung University, Tainan 701, Taiwan.
authors.forename: Xin-Yu
authors.initials: XY
authors.lastname: Chen
authors.affiliation: Department of Life Sciences, National University of Kaohsiung, Kaohsiung 811, Taiwan.
authors.forename: Chiu-Ming
authors.initials: CM
authors.lastname: Wen
authors.affiliation: Laboratory of Marine Molecular Biology and Biotechnology, Institute of Cellular and Organismic Biology, Academia Sinica, Nankang, Taipei 115, Taiwan.
authors.forename: Cho-Fat
authors.initials: CF
authors.lastname: Hui
authors.affiliation: Department of Marine Biotechnology, National Kaohsiung Marine University, Kaohsiung 811, Taiwan.
authors.forename: Ming-Chyuan
authors.initials: MC
authors.lastname: Chen
authors.affiliation: Laboratory of Marine Molecular Biology and Biotechnology, Institute of Cellular and Organismic Biology, Academia Sinica, Nankang, Taipei 115, Taiwan.
authors.forename: Jen-Leih
authors.initials: JL
authors.lastname: Wu
authors.affiliation: Laboratory of Molecular Virology and Biotechnology, Institute of Biotechnology, National Cheng-Kung University, Tainan 701, Taiwan.
authors.forename: Tsai-Ching
authors.initials: TC
authors.lastname: Hsueh
authors.affiliation: Laboratory of Molecular Virology and Biotechnology, Institute of Biotechnology, National Cheng-Kung University, Tainan 701, Taiwan.
authors.forename: Wei-Han
authors.initials: WH
authors.lastname: Lei
authors.affiliation: Laboratory of Molecular Virology and Biotechnology, Institute of Biotechnology, National Cheng-Kung University, Tainan 701, Taiwan. Electronic address: jrhong@mail.ncku.edu.tw.
authors.forename: Jiann-Ruey
authors.initials: JR
authors.lastname: Hong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001492:Bass; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D004266:DNA Virus Infections / Q000235:genetics / Q000378:metabolism / Q000662:veterinary* / Q000821:virology; D005393:Fish Diseases / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D029941:Fish Proteins / Q000235:genetics* / Q000378:metabolism; D017994:Iridovirus / Q000502:physiology; D053078:Membrane Potential, Mitochondrial; D015854:Up-Regulation; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics* / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: D029941:Fish Proteins; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D053148:Caspase 3
keywords: Bak; Bax; Bcl-xL; Iridovirus; Overexpression; Pro-apoptotic gene; Upregulation