The nonstructural proteins of Nipah virus play a key role in pathogenicity in experimentally infected animals.
The nonstructural proteins of Nipah virus play a key role in pathogenicity in experimentally infected animals.
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DOI：
10.1371/journal.pone.0012709
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发表时间：
2010-09-15
期刊：
影响因子：
3.7
通讯作者：
Kai C
中科院分区：
文献类型：
--
作者：
Yoneda M;Guillaume V;Sato H;Fujita K;Georges-Courbot MC;Ikeda F;Omi M;Muto-Terao Y;Wild TF;Kai C
尼帕病毒 (NiV) P 基因编码 P 蛋白和三种辅助蛋白（V、C 和 W）。据报道，当蛋白质瞬时表达时，所有四种P基因产物均具有IFN拮抗剂活性。然而，这些辅助蛋白在 NiV 自然感染中的作用仍不清楚。我们分别生成了缺乏 V、C 或 W 蛋白的重组 NiV、rNiV(V−)、rNiV(C−) 和 rNiV(W−)，以分析这些蛋白在感染细胞中的功能及其对体内致病性的影响。尽管rNiV(V−)和rNiV(C−)的最大滴度低于其他重组体，但所有重组体在细胞培养物中均生长良好。 rNiV(V−)、rNiV(C−) 和 rNiV(W−) 与亲本 rNiV 一样抑制 IFN 反应，从而表明每种辅助蛋白的缺乏不会显着影响受感染细胞中 IFN 信号传导的抑制。在实验感染的金仓鼠中，rNiV(V−) 和 rNiV(C−) 但 rNiV(W−) 病毒的毒力没有显着降低。这些结果表明，V 和 C 蛋白在 NiV 致病性中发挥关键作用，并且这些作用与其 IFN 拮抗剂活性无关。这是第一份鉴定 NiV 体内致病性分子决定因素的报告。
Nipah virus (NiV) P gene encodes P protein and three accessory proteins (V, C and W). It has been reported that all four P gene products have IFN antagonist activity when the proteins were transiently expressed. However, the role of those accessory proteins in natural infection with NiV remains unknown. We generated recombinant NiVs lacking V, C or W protein, rNiV(V−), rNiV(C−), and rNiV(W−), respectively, to analyze the functions of these proteins in infected cells and the implications in in vivo pathogenicity. All the recombinants grew well in cell culture, although the maximum titers of rNiV(V−) and rNiV(C−) were lower than the other recombinants. The rNiV(V−), rNiV(C−) and rNiV(W−) suppressed the IFN response as well as the parental rNiV, thereby indicating that the lack of each accessory protein does not significantly affect the inhibition of IFN signaling in infected cells. In experimentally infected golden hamsters, rNiV(V−) and rNiV(C−) but not the rNiV(W−) virus showed a significant reduction in virulence. These results suggest that V and C proteins play key roles in NiV pathogenicity, and the roles are independent of their IFN-antagonist activity. This is the first report that identifies the molecular determinants of NiV in pathogenicity in vivo.
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