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

对乙型脑炎病毒致病因素进行了分析。采用原代大鼠脑培养和建立的细胞系，获得了以下结果。1.乙型脑炎病毒可感染神经元并复制，但不能感染神经胶质细胞。2.乙型脑炎病毒可吸附并复制在未成熟神经元上，但不能吸附在已分化的成熟神经元上完成突触形成。3.乙型脑炎病毒在敏感细胞上能有效吸附和内化，而在不敏感细胞上不能有效吸附和内化。4.乙型脑炎病毒可以在不敏感的细胞中复制，这些细胞直接被感染的RNA进入细胞质。5.从日本脑炎病毒易感细胞膜部分中分离到一种能与乙脑病毒E蛋白结合的75Kd受体候选分子。通过对日本脑炎病毒…颗粒形成机制的分析，得到以下结果更多的是病毒。1.多聚体蛋白在内质网腔内表达和加工后形成包膜上的PRM-E异源二聚体，经高尔基复合体处理后以成熟病毒粒子的形式从感染细胞中释放出来。2.在低pH条件下，M-E异源二聚体转化为E均三聚体。3.在病毒粒子与细胞受体结合完成后，E蛋白上的这种结构变化可诱导病毒粒子的包膜与敏感细胞的细胞膜发生融合。4.PrM蛋白的C末端具有形成PrM-E异源二聚体、构建E蛋白结构和E蛋白在细胞内转运所必需的孔洞。5.中和表位氨基酸替换导致乙型脑炎病毒神经毒力下降。这些结果表明，乙型脑炎病毒神经毒力的一部分决定于易感细胞上的细胞受体与病毒粒子的E蛋白和PrM蛋白的结合效率，E蛋白结构的构建对病毒与受体和细胞膜的反应性起关键作用。较少

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