title: Giant seaperch iridovirus (GSIV) induces mitochondria-mediated cell death that is suppressed by bongkrekic acid and cycloheximide in a fish cell line.
abstract: Giant seaperch iridovirus (GSIV) induces cell death by an unknown mechanism. We postulated that this mechanism involves mitochondria-mediated cell death. Cell viability assays revealed a steady increase in dead grouper fin cells (GF-1) after GSIV infection, from 11% at 2 days post-infection (dpi) to 67% at 5 dpi. Annexin V/PI staining revealed GSIV infection induced apoptosis in a steadily increasing fraction of cells, from 4% at 1 dpi to 29% at 5 dpi. Furthermore, post-apoptotic necrosis was apparent at 4 and 5 dpi in the late replication stage. In the early replication stage, JC-1 dye revealed mitochondrial membrane potential (ΔΨm) loss in 42% of infected cells at 1 dpi, increasing to 98% at 3 dpi. Phosphatidylserine (PS) exposure and loss of ΔΨm from apoptosis/necrosis was attenuated by treatment with the adenine nucleotide translocase inhibitor bongkrekic acid (BKA) and the protein synthesis inhibitor cyclohexamide (CHX). These data suggest GSIV induces GF-1 apoptotic/necrotic cell death through pathways that require newly synthesized protein and involve the mitochondrial function.
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: 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: Yu-Chin
authors.initials: YC
authors.lastname: Su
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; D000998:Antiviral Agents / Q000494:pharmacology*; D001865:Bongkrekic Acid / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects*; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology*; D005399:Fishes; D054884:Host-Pathogen Interactions / Q000187:drug effects*; D017994:Iridovirus / Q000187:drug effects*; D008928:Mitochondria / Q000378:metabolism*
chemical_list: D000998:Antiviral Agents; D001865:Bongkrekic Acid; D003513:Cycloheximide
keywords: Bongkrekic acid; De novo; Iridovirus; Mitochondria; Mitochondrial membrane potential loss; Synthesized protein