The viral TRAF protein (ORF111L) from infectious spleen and kidney necrosis virus interacts with TRADD and induces caspase 8-mediated apoptosis.
The viral TRAF protein (ORF111L) from infectious spleen and kidney necrosis virus interacts with TRADD and induces caspase 8-mediated apoptosis.
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DOI：
10.1371/journal.pone.0037001
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
He JG
中科院分区：
文献类型：
--
作者：
He BL;Yuan JM;Yang LY;Xie JF;Weng SP;Yu XQ;He JG
传染性脾肾坏死病毒（ISKNV）是虹彩病毒科巨细胞病毒属的模式种。它在野生和养殖鱼类中引起严重的和潜在的大流行性疾病。ISKNV感染引起了鳜鱼和斑马鱼明显的细胞凋亡。然而，其机制仍然未知。对ISKNV编码的蛋白质进行全基因组生物信息学分析后，ISKNV开放阅读框111 L（ORF 111 L）与鱼类、小鼠和哺乳动物编码的肿瘤坏死因子受体相关因子（TRAF）高度相似，这对于细胞凋亡信号传导至关重要。此外，ORF 111 L被证实直接与斑马鱼TNF受体1型相关死亡结构域蛋白（TRADD）相互作用。构建了含有ORF 111 L基因的重组质粒，并将其注射到1-2细胞期的斑马鱼胚胎中，研究其在体内的生物学功能。ORF 111 L在胚胎中的过表达导致细胞凋亡增加。ORF 111 L诱导的细胞凋亡明显与caspase 8的显著上调和激活相关。下调caspase 8的表达可有效地阻断ORF 111 L过表达诱导的细胞凋亡。值得注意的是，与斑马鱼TRAF 2相比，ORF 111 L过表达对caspase 8和caspase 3上调的影响更强。这是第一个报告的病毒蛋白类似TRAF与TRADD相互作用，并诱导caspase 8介导的细胞凋亡，这可能提供新的见解ISKNV感染的发病机制。
Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the Megalocytivirus genus of the Iridoviridae family. It causes a serious and potentially pandemic disease in wild and cultured fishes. ISKNV infection induces evident apoptosis in mandarin fish (Siniperca chuatsi) and zebrafish (Danio renio). However, the mechanism is still unknown. After a genome-wide bioinformatics analysis of ISKNV-encoded proteins, the ISKNV open reading frame 111L (ORF111L) shows a high similarity to the tumour necrosis factor receptor-associated factor (TRAF) encoded by fish, mice and mammals, which is essential for apoptotic signal transduction. Moreover, ORF111L was verified to directly interact with the zebrafish TNF receptor type 1 associated death domain protein (TRADD). A recombinant plasmid containing the DNA sequence of ORF111L was constructed and microinjected into zebrafish embryos at the 1–2 cell stage to investigate its biological function in vivo. ORF111L overexpression in the embryos resulted in increased apoptosis. ORF111L-induced apoptosis was clearly associated with significant caspase 8 upregulation and activation. The knockdown of zebrafish caspase 8 expression effectively blocked the apoptosis induced by ORF111L overexpression. Significantly, ORF111L overexpression resulted in much stronger effect on caspase 8 and caspase 3 upregulation compared to zebrafish TRAF2. This is the first report of a viral protein similar to TRAF that interacts with TRADD and induces caspase 8-mediated apoptosis, which may provide novel insights into the pathogenesis of ISKNV infection.
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