title: Involvement of the PI3K and ERK signaling pathways in largemouth bass virus-induced apoptosis and viral replication.
abstract: Increased reports demonstrated that largemouth Bass, Micropterus salmoides in natural and artificial environments were always suffered from an emerging iridovirus disease, largemouth Bass virus (LMBV). However, the underlying mechanism of LMBV pathogenesis remained largely unknown. Here, we investigated the cell signaling events involved in virus induced cell death and viral replication in vitro. We found that LMBV infection in epithelioma papulosum cyprini (EPC) cells induced typical apoptosis, evidenced by the appearance of apoptotic bodies, cytochrome c release, mitochondrial membrane permeabilization (MMP) destruction and reactive oxygen species (ROS) generation. Two initiators of apoptosis, caspase-8 and caspase-9, and the executioner of apoptosis, caspase-3, were all significantly activated with the infection time, suggested that not only mitochondrion-mediated, but also death receptor-mediated apoptosis were involved in LMBV infection. Reporter gene assay showed that the promoter activity of transcription factors including p53, NF-κB, AP-1 and cAMP response element-binding protein (CREB) were decreased during LMBV infection. After treatment with different signaling pathway inhibitors, virus production were significantly suppressed by the inhibition of phosphatidylinositol 3-kinase (PI3K) pathway and extracellular-signal-regulated kinases (ERK) signaling pathway. Furthermore, LMBV infection induced apoptosis was enhanced by PI3K inhibitor LY294002, but decreased by addition of ERK inhibitor UO126. Therefore, we speculated that apoptosis was sophisticatedly regulated by a series of cell signaling events for efficient virus propagation. Taken together, our results provided new insights into the molecular mechanism of ranavirus infection.
authors.affiliation: Key Laboratory of Tropical Marine Bio-resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China; University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Huang
authors.affiliation: Key Laboratory of Tropical Marine Bio-resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China; University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Key Laboratory of Tropical Marine Bio-resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China; University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Youhua
authors.initials: Y
authors.lastname: Huang
authors.affiliation: South China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, Guangdong 510300, China.
authors.forename: Liwen
authors.initials: L
authors.lastname: Xu
authors.affiliation: Key Laboratory of Tropical Marine Bio-resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China; University of Chinese Academy of Sciences, Beijing, China. Electronic address: qinqw@scsio.ac.cn.
authors.forename: Qiwei
authors.initials: Q
authors.lastname: Qin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001492:Bass; D020169:Caspases / Q000378:metabolism; D004266:DNA Virus Infections / Q000503:physiopathology / Q000662:veterinary*; D005393:Fish Diseases / Q000503:physiopathology* / Q000821:virology*; D005434:Flow Cytometry / Q000662:veterinary; D066298:In Vitro Techniques; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008856:Microscopy, Fluorescence / Q000662:veterinary; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D017995:Ranavirus; D017382:Reactive Oxygen Species / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology
chemical_list: D017382:Reactive Oxygen Species; D019869:Phosphatidylinositol 3-Kinases; D020169:Caspases
keywords: Apoptosis; ERK signaling pathway; LMBV; Largemouth bass; PI3K signaling pathway