CyHV-2 ORF104 activates the p38 MAPK pathway
CyHV-2 ORF104 activates the p38 MAPK pathway
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CyHV-2 ORF104 激活 p38 MAPK 通路。
DOI：
10.1016/j.fsi.2015.06.011
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发表时间：
2015-10-01
影响因子：
4.7
通讯作者：
Chen, Jianming
中科院分区：
文献类型：
--
作者：
Du, Mi;Chen, Mingliang;Chen, Jianming
鲤疱疹病毒2型（CyHV-2）是引起鲤疱疹病毒性造血细胞坏死病的病原，给水产养殖业造成巨大损失。目前对CyHV-2的研究主要集中在该病毒的鉴定和检测上，但对CyHV-2特异性基因在感染过程中的作用知之甚少。基于基因组信息，CyHV-2 ORF 104编码激酶样蛋白，其在三种CyHV中高度保守。我们的研究旨在探讨激酶样蛋白ORF 104在病毒感染过程中的作用。亚细胞定位研究表明ORF 104在人HEK 293 T和鱼EPC细胞中主要表达于细胞核。然而，ORF 104（ORF 104 M）的假定核定位信号的缺失导致HEK 293 T中的细胞质分布。然后，我们通过在HEK 293 T中过表达ORF 104和ORF 104 M来检测MAPK是否参与ORF 104介导的信号通路。ORF 104和ORF 104 M的过表达导致p38磷酸化水平上调，而JNK和ERK的磷酸化水平没有上调，表明ORF 104特异性激活p38信号通路。体内研究表明，CyHV-2感染增强了异育银鲫（Carassius auratus gibelio）p38的磷酸化。有趣的是，p38抑制剂SB 203580强烈降低了CyHV-2感染引起的鱼类死亡。因此，我们的研究首次揭示了ORF 104在CyHV-2感染过程中的功能，表明ORF 104是CyHV-2的潜在候选疫苗。(C)2015爱思唯尔有限公司版权所有。
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. (C) 2015 Elsevier Ltd. All rights reserved.