title: CyHV-2 ORF104 activates the p38 MAPK pathway.
abstract: Cyprinid herpesvirus 2 (CyHV-2) is the pathogen responsible for herpesviral hematopoietic necrosis disease, which causes huge losses on aquaculture. So far the studies of CyHV-2 mainly focus on the identification and detection of this virus, but little is known about the role of specific CyHV-2 genes in the infection process. Based on the genomic information, CyHV-2 ORF104 encodes a kinase-like protein, which is highly conserved among the three CyHVs. Our study was initiated to investigate the role of kinase-like protein ORF104 during virus infection. Subcellular localization study showed that ORF104 was mainly expressed in the nucleus in both human HEK293T and fish EPC cells. However, deletion of the putative nuclear localization signal of ORF104 (ORF104M) resulted in the cytoplasmic distribution in HEK293T. We then examined whether MAPKs were involved in the ORF104-mediated signaling pathway by overexpressing ORF104 and ORF104M in HEK293T. Overexpression of ORF104 and ORF104M resulted in the up-regulation of p38 phosphorylation, but not JNK or ERK, indicating that ORF104 specifically activates p38 signaling pathway. In vivo study showed that CyHV-2 infection enhanced p38 phosphorylation in gibel carp (Carassius auratus gibelio). Interestingly, p38 inhibitor SB203580 strongly reduced fish death caused by CyHV-2 infection. Therefore, our study for the first time reveals the function of ORF104 during CyHV-2 infection, indicating that ORF104 is a potential vaccine candidate for CyHV-2.
authors.affiliation: School of Marine Sciences, Ningbo University, Ningbo, 315211 Zhejiang, China; State Key Laboratory Breeding Base of Marine Genetic Resources, South China Sea Bio-Resource Exploitation and Utilization Collaborative Innovation Center, Third Institute of Oceanography, State Oceanic Administration, Xiamen, 361005 Fujian, China.
authors.forename: Mi
authors.initials: M
authors.lastname: Du
authors.affiliation: State Key Laboratory Breeding Base of Marine Genetic Resources, South China Sea Bio-Resource Exploitation and Utilization Collaborative Innovation Center, Third Institute of Oceanography, State Oceanic Administration, Xiamen, 361005 Fujian, China.
authors.forename: Mingliang
authors.initials: M
authors.lastname: Chen
authors.affiliation: State Key Laboratory Breeding Base of Marine Genetic Resources, South China Sea Bio-Resource Exploitation and Utilization Collaborative Innovation Center, Third Institute of Oceanography, State Oceanic Administration, Xiamen, 361005 Fujian, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Shen
authors.affiliation: State Key Laboratory Breeding Base of Marine Genetic Resources, South China Sea Bio-Resource Exploitation and Utilization Collaborative Innovation Center, Third Institute of Oceanography, State Oceanic Administration, Xiamen, 361005 Fujian, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: State Key Laboratory Breeding Base of Marine Genetic Resources, South China Sea Bio-Resource Exploitation and Utilization Collaborative Innovation Center, Third Institute of Oceanography, State Oceanic Administration, Xiamen, 361005 Fujian, China.
authors.forename: Zengpeng
authors.initials: Z
authors.lastname: Li
authors.affiliation: State Key Laboratory Breeding Base of Marine Genetic Resources, South China Sea Bio-Resource Exploitation and Utilization Collaborative Innovation Center, Third Institute of Oceanography, State Oceanic Administration, Xiamen, 361005 Fujian, China.
authors.forename: Weiyi
authors.initials: W
authors.lastname: Wang
authors.affiliation: Putian Aquatic Products, Technical Extension Station, Putian, 351100 Fujian, China.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Huang
authors.affiliation: State Key Laboratory Breeding Base of Marine Genetic Resources, South China Sea Bio-Resource Exploitation and Utilization Collaborative Innovation Center, Third Institute of Oceanography, State Oceanic Administration, Xiamen, 361005 Fujian, China. Electronic address: chenjm@xmu.edu.cn.
authors.forename: Jianming
authors.initials: J
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004266:DNA Virus Infections / Q000662:veterinary* / Q000821:virology; D004267:DNA Viruses / Q000235:genetics* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005393:Fish Diseases / Q000821:virology*; D029941:Fish Proteins / Q000235:genetics / Q000378:metabolism; D006054:Goldfish; D007093:Imidazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D016415:Sequence Alignment / Q000662:veterinary; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D029941:Fish Proteins; D007093:Imidazoles; D011725:Pyridines; D014764:Viral Proteins; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580
keywords: Cyprinid herpesvirus 2; Gibel carp; ORF104; p38