betanodavirus induces oxidative stress-mediated cell death that prevented by anti-oxidants and zfcatalase in fish cellsbetanodavirus诱发氧化stress-mediated细胞死亡,阻止细胞抗氧化剂和zfcatalase鱼.pdfVIP

Betanodavirus Induces Oxidative Stress-Mediated Cell Death That Prevented by Anti-Oxidants and Zfcatalase in Fish Cells 1 1 2 3 1 Chih-Wei Chang , Yu-Chin Su , Guor-Mour Her , Chuian-Fu Ken , Jiann-Ruey Hong * 1 Laboratory of Molecular Virology and Biotechnology, Institute of Biotechnology, National Cheng Kung University, Tainan, Taiwan, Republic of China, 2 Institute of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, Taiwan, Republic of China, 3 The Department of Biotechnology, National Changhua University of Education, Changhua, Taiwan, Republic of China Abstract The role of oxidative stress in the pathogenesis of RNA nervous necrosis virus infection is still unknown. Red-spotted grouper nervous necrosis virus (RGNNV) induced free radical species (ROS) production at 12–24 h post-infection (pi; early replication stage) in fish GF-1 cells, and then at middle replication stage (24–48 h pi), this ROS signal may upregulate some expressions of the anti-oxidant enzymes Cu/Zn SOD and catalase, and eventually expression of the transcription factor Nrf2. Furthermore, both antioxidants diphenyliodonium and N-acetylcysteine or overexpression of zebrafish catalase in GF-1 cells also reduced ROS production and protected cells for enhancing host survival rate due to RGNNV infection. Furthermore, localization of ROS production using esterase activity and Mitotracker staining assays found that the ROS generated can affect mitochondrial morphology changes and causes DY loss, both of which can be reversed by antioxidant treatment. Taken together, our data suggest that RGNNV induced oxidative stress response for playing dual role that can initiate the host oxidative stress defense system to upr