title: The viral TRAF protein (ORF111L) from infectious spleen and kidney necrosis virus interacts with TRADD and induces caspase 8-mediated apoptosis.
abstract: 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.
authors.affiliation: MOE Key Laboratory of Aquatic Product Safety/State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Bai-Liang
authors.initials: BL
authors.lastname: He
authors.forename: Ji-Min
authors.initials: JM
authors.lastname: Yuan
authors.forename: Lu-Yun
authors.initials: LY
authors.lastname: Yang
authors.forename: Jun-Feng
authors.initials: JF
authors.lastname: Xie
authors.forename: Shao-Ping
authors.initials: SP
authors.lastname: Weng
authors.forename: Xiao-Qiang
authors.initials: XQ
authors.lastname: Yu
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: He
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods; D004279:DNA, Viral / Q000235:genetics; D005393:Fish Diseases / Q000235:genetics / Q000378:metabolism / Q000821:virology; D007497:Iridoviridae / Q000235:genetics / Q000378:metabolism*; D016366:Open Reading Frames; D053199:TNF Receptor-Associated Death Domain Protein / Q000235:genetics / Q000378:metabolism; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000235:genetics* / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish
chemical_list: D004279:DNA, Viral; D053199:TNF Receptor-Associated Death Domain Protein; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D014764:Viral Proteins; D053148:Caspase 3; D053181:Caspase 8