日本乙型脑炎病毒（JEV）E蛋白位点突变能介导其神经毒力改变，但其感染机理尚不清楚。我们前期证实JEV E-I176R位点突变显著降低其神经毒力，推测可能与细胞受体、膜融合、病毒增殖和致炎症损伤等有关。为阐明JEV E-I176R位点突变减弱其神经毒力的感染机理，本研究以突变株(JEV E-I176R)和亲本株(JEV E-I176I)为材料，体外试验感染鼠小胶质细胞，首先进行病毒吸附内吞、病毒结合受体和膜融合试验，探究病毒入侵细胞差异；其次测定JEV生长曲线，IFA测定病毒E蛋白，探析病毒复制增殖差异；最后qRT-PCR等检测TNF-α、IFN-α、IL-6等炎性细胞因子，探明病毒诱导细胞因子差异。体内试验感染BALB/c小鼠，分别进行噬斑试验测定鼠脑病毒含量、切片检测鼠脑炎性损伤、免疫组化检测鼠脑病毒载量等，探析病毒体内复增殖、致炎损伤差异。本研究对阐明JEV神经毒力机理具有重要意义。

Japanese encephalitis virus (JEV) E protein site mutation can mediate its neurovirulence, but the infection mechanism of its neurovirulence remains unknown. We previously confirmed that JEV E-I176R site mutation reduced its neurovirulence, which may be related to cell receptors, membrane fusion, virus propagation and inflammatory damage. In this study, mutant strain (JEV E-I176R) and parental strain (JEV E-I176I) were used as materials to elucidate the mechanism of neurovirulence attenuated by mutation at the JEV E-I176R. In vitro, JEV infects the mouse microglial cells, first, we carry on the virus binding and internalization assay, virus-receptor interaction assay and membrane fusion test to explore the differences of invasion between two virus strain; Secondly, the growth curve of JEV was determined, and the viral E protein was determined by IFA to explore the differences of virus replication and proliferation; Finally, qRT-PCR and other methods were used to detect TNF-α, IFN-α, IL-6 and other inflammatory cytokines to investigate the differences in virus-induced cytokines. In vivo, BALB/c mice were infected with two JEV strains, by determining the content of virus in brain with plaque forming assay, verifying the inflammatory injury in brain with pathological section and detecting the viral load of brain with immunohistochemistry, we are going to explore the differences in virus proliferation and inflammatory injury. This study is of great significance to elucidate the neurovirulence mechanism of JEV virus.