VP08R from infectious spleen and kidney necrosis virus is a novel component of the virus-mock basement membrane.
VP08R from infectious spleen and kidney necrosis virus is a novel component of the virus-mock basement membrane.
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来自传染性脾肾坏死病毒的 VP08R 是病毒模拟基底膜的新成分。
DOI：
10.1128/jvi.03776-13
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发表时间：
2014
影响因子：
5.4
通讯作者：
He Jian-Guo
中科院分区：
文献类型：
--
作者：
Xu Xiaopeng;Yan Muting;Wang Rui;Lin Ting;Tang Junliang;Li Chaozheng;Weng Shaoping;He Jian-Guo
传染性脾肾坏死病毒(ISKNV)是虹膜病毒科巨细胞病毒属的模式种，给养殖业带来极大危害。在被感染的组织中，ISKNV感染具有一个独特的现象，即被感染的细胞被淋巴管内皮细胞(LECs)附着，淋巴管内皮细胞被认为是隔离被感染细胞免受宿主免疫攻击的细胞。病毒膜蛋白VP23R结合并招募宿主Nidogen-1蛋白，在感染细胞表面构建一个类似基底膜(BM)的结构，称为病毒模拟基底膜(VMBM)，为LECs提供附着位置。VMBM不包含IV型胶原蛋白，而IV型胶原蛋白是维持BM完整性和功能所必需的。在本研究中，我们鉴定了ISKNV编码的VP08R蛋白。预测VP08R是一种分泌型蛋白，含有信号肽，但不含跨膜区。免疫荧光分析表明，VP08R定位于感染细胞的质膜上，表达谱与VP23R相似。免疫共沉淀结果表明，VP08R与VP23R和Nidogen-1均有相互作用，表明VP08R是VMBM的一种成分，通过与VP23R结合存在于细胞膜上。通过分子间二硫键的形成，VP08R分子自组织形成多聚体，可能在维持VMBM的完整性和稳定性中发挥作用。此外，VP08R多聚体在裂解ISKNV感染的细胞时容易被降解，这可能是VMBM在需要时解离以释放成熟病毒的机制。传染性脾肾坏死病毒(ISKNV；虹彩病毒科巨细胞病毒属)对养殖鱼的危害最大。在组织中，被ISKNV感染的细胞被淋巴管内皮细胞(LECs)附着，LECs被认为是隔离宿主免疫系统的细胞。病毒膜蛋白VP23R结合并募集宿主Nidogen-1蛋白，在感染细胞表面构建病毒模拟基底膜，为LECs提供附着部位。尽管VMBMS缺乏IV型胶原网络，这是真正的BMS的重要结构部分，但VMBMS仍然显示出完整的结构。ISKNV编码的VP08R蛋白可以自组装成多聚体，并与VP23R和Nidgen-1结合，以维持VMBMS的完整性和稳定性。基于这些事实，我们重新绘制了VMBM结构的假定示意图。我们的研究表明，该病毒采用了一种重塑细胞基质的策略，可能为阐明BM的功能和淋巴管生成机制提供重要参考。
Infectious spleen and kidney necrosis virus (ISKNV), the type species of the genus Megalocytivirus, family Iridoviridae, brings great harm to fish farming. In infected tissues, ISKNV infection is characterized by a unique phenomenon, in that the infected cells are attached by lymphatic endothelial cells (LECs), which are speculated to wall off the infected cells from host immune attack. A viral membrane protein, VP23R, binds and recruits the host nidogen-1 protein to construct a basement membrane (BM)-like structure, termed virus-mock basement membrane (VMBM), on the surface of infected cells to provide attaching sites for LECs. VMBMs do not contain collagen IV protein, which is essential for maintenance of BM integrity and functions. In this study, we identified the VP08R protein encoded by ISKNV. VP08R was predicted to be a secreted protein with a signal peptide but without a transmembrane domain. However, immunofluorescence assays demonstrated that VP08R is located on the plasma membrane of infected cells and shows an expression profile similar to that of VP23R. Coimmunoprecipitation showed that VP08R interacts with both VP23R and nidogen-1, indicating that VP08R is a component of VMBM and is present on the cell membrane by binding to VP23R. Through formation of intermolecular disulfide bonds, VP08R molecules self-organized into a multimer, which may play a role in the maintenance of VMBM integrity and stability. Moreover, the VP08R multimer was easily degraded when the ISKNV-infected cells were lysed, which may be a mechanism for VMBM disassembly when necessary to free LECs and release the mature virions.IMPORTANCEInfectious spleen and kidney necrosis virus (ISKNV; genus Megalocytivirus, family Iridovirus) is most harmful to cultured fishes. In tissues, the ISKNV-infected cells are attached by lymphatic endothelial cells (LECs), which are speculated to segregate the host immune system. A viral membrane protein, VP23R, binds and recruits the host nidogen-1 protein to construct virus-mock basement membranes (VMBMs) on the surface of infected cells to provide attaching sites for LECs. Although VMBMs lack the collagen IV network, which is an essential structural part of true BMs, VMBMs still show an intact structure. An ISKNV-encoded VP08R protein can self-assemble into a multimer and bind both VP23R and nidogen-1 to maintain the integrity and stability of VMBMs. On the basis of these facts, we redrew the putative schematic illustration of the VMBM structure. Our study suggests that the virus adopts a strategy to remodel the cellular matrix and may provide an important reference to elucidate BM functions and the mechanisms of lymphangiogenesis.