title: Singapore grouper iridovirus, a large DNA virus, induces nonapoptotic cell death by a cell type dependent fashion and evokes ERK signaling.
abstract: Virus induced cell death, including apoptosis and nonapoptotic cell death, plays a critical role in the pathogenesis of viral diseases. Singapore grouper iridovirus (SGIV), a novel iridovirus of genus Ranavirus, causes high mortality and heavy economic losses in grouper aquaculture. Here, using fluorescence microscopy, electron microscopy and biochemical assays, we found that SGIV infection in host (grouper spleen, EAGS) cells evoked nonapoptotic programmed cell death (PCD), characterized by appearance of cytoplasmic vacuoles and distended endoplasmic reticulum, in the absence of DNA fragmentation, apoptotic bodies and caspase activation. In contrast, SGIV induced typical apoptosis in non-host (fathead minnow, FHM) cells, as evidenced by caspase activation and DNA fragmentation, suggesting that SGIV infection induced nonapoptotic cell death by a cell type dependent fashion. Furthermore, viral replication was essential for SGIV induced nonapoptotic cell death, but not for apoptosis. Notably, the disruption of mitochondrial transmembrane potential (ΔΨm) and externalization of phosphatidylserine (PS) were not detected in EAGS cells but in FHM cells after SGIV infection. Moreover, the extracellular signal-regulated kinase (ERK) signaling was involved in SGIV infection induced nonapoptotic cell death and viral replication. This is a first demonstration of ERK-mediated nonapoptotic cell death induced by a DNA virus. These findings contribute to understanding the mechanisms of iridovirus pathogenesis.
authors.affiliation: Key Laboratory of Marine Bio-Resources Sustainable Utilization, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Huang
authors.forename: Youhua
authors.initials: Y
authors.lastname: Huang
authors.forename: Zhengliang
authors.initials: Z
authors.lastname: Ouyang
authors.forename: Lixiao
authors.initials: L
authors.lastname: Xu
authors.forename: Yang
authors.initials: Y
authors.lastname: Yan
authors.forename: Huachun
authors.initials: H
authors.lastname: Cui
authors.forename: Xin
authors.initials: X
authors.lastname: Han
authors.forename: Qiwei
authors.initials: Q
authors.lastname: Qin
mesh_terms: D000818:Animals; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003530:Cyprinidae / Q000821:virology; D053938:DNA Fragmentation; D004266:DNA Virus Infections / Q000503:physiopathology*; D004721:Endoplasmic Reticulum / Q000473:pathology / Q000648:ultrastructure; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D029941:Fish Proteins / Q000235:genetics / Q000378:metabolism*; D017994:Iridovirus / Q000502:physiology*; D020935:MAP Kinase Signaling System; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000473:pathology / Q000648:ultrastructure; D010473:Perciformes / Q000821:virology*; D010718:Phosphatidylserines / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D029941:Fish Proteins; D010718:Phosphatidylserines; D017382:Reactive Oxygen Species; D048049:Extracellular Signal-Regulated MAP Kinases; D020169:Caspases