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Analysis of Neurovirulence of Japanese encephalitis virus based on Eprotein-receptor interaction

基于E蛋白-受体相互作用的乙型脑炎病毒神经毒力分析

基本信息

批准号：
04454204
负责人：
YASUI Kotaro
金额：
$ 4.22万
依托单位：
TOKYO METROPOLITAN INSTITUTE FOR NEUROSCIENCES
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04454204/
关键词：
Japanese encephalitis virus neurovirulence neuron cellular receptor E protein prM protein エンベロープ E-Mヘテロ2量体 E蛋白のホモ3量体レセプター分子感受性細胞受容体 M蛋白 preM蛋白 E蛋白構造

项目摘要

Factors which participated in the pathogenicity of Japanese encephalitis virus were analyzed.The following results were obtained using primary rat brain culture and established cell lines. 1. Japanese encephalitis virus could infect and replicate in neurons but not in glial cells. 2. Japanese encephalitis virus could be adsorbed and replicate on immature neurons but not on differentiated mature neurons which completed synapse formation. 3. Japanese encephalitis virus could be adsorbed and internalized effectively on susceptible cells but not on unsusceptible cells. 4. Japanese encephalitis virus could replicate in unsusceptible cells which were received the infectious RNA directly into the cytoplasm. 5. A candidate 75Kd receptor molecule which could bind with the E protein of Japanese encephalitis virus was detected and isolated from membrane fractions of susceptible cells.The following results were obtained from an analysis on the mechanism of particle formation of Japanese encephalit … More is virus. 1. A prM-E heterodimer on an envelope was formed after expression and processing of polyprotein in ER lumen and the prM protein was processed in golgi complex and then the M-E heterodimer on the envelope was released from infected cells as a mature virion. 2. The M-E heterodimer was converted to E homotrimer under low pH conditions. 3. This structural change occurred on the E protein could induce a fusion between the envelope of the virion and cell membranes of susceptible cells after the virion and the cellular receptor binding was completed. 4. The C terminal part of prM protein had essential Hole for the formation of the prM-E heterodimer and the construction of the E protein structure and the transport of the E protein in the cells. 5. Amino acid replacements at the neutralizing epitope induced decreased neurovirulence on the virus.These results indicate that a part of neurovirulence of Japanese encephalitis virus is determined the binding efficiency between the cellular receptor on the susceptible cells and the E protein of the virion and prM protein has a critical role on the construction of the E protein structure responsible on the reactivity with the receptor and the cell membranes. Less

本研究利用大鼠脑组织原代培养和建立的细胞系，分析了乙型脑炎病毒致病性的相关因素。1.乙脑病毒可在神经元中感染和复制，但不能在胶质细胞中感染和复制。2.乙脑病毒可在未成熟的神经元上吸附和复制，但在已分化的成熟神经元上不能吸附和复制。3.乙脑病毒在易感细胞上能有效地吸附和内化，而在非易感细胞上不能。4.感染性RNA直接进入细胞质后，乙脑病毒可在非易感细胞中复制。5.从日本脑炎病毒易感细胞膜组分中分离到一个与病毒E蛋白结合的75 Kd受体分子，并对病毒颗粒形成机制进行了分析， ...更多信息是病毒1.多聚蛋白在内质网腔表达加工后，在被膜上形成prM-E异二聚体，prM蛋白在高尔基复合体中被加工后，被膜上的M-E异二聚体作为成熟病毒体从感染细胞中释放出来。2. M-E异二聚体在低pH条件下转化为E同三聚体。3. E蛋白发生的这种结构变化，在病毒粒子与细胞受体结合完成后，可诱导病毒粒子的包膜与易感细胞的细胞膜融合。4. prM蛋白C端有一个Hole，它对prM-E异源二聚体的形成、E蛋白结构的构建以及E蛋白在细胞内的转运都是必不可少的。5.这些结果表明，乙脑病毒的神经毒力部分取决于易感细胞上的细胞受体与病毒粒子上E蛋白的结合效率，而prM蛋白对E蛋白结构的构建起关键作用，E蛋白结构负责与受体和细胞膜的反应。少