不同狂犬病病毒对胶质细胞功能影响的研究
发布时间：2018-08-14 18:45
【摘要】：狂犬病(Rabies)是由狂犬病病毒(Rabies virus,RABV)引起的一种高死亡率的人畜共患病,能引起人和其它哺乳动物的大脑炎症。RABV具有高度的嗜神经性,目前人狂犬病病例主要是通过携带病毒的犬咬伤传播。RABV到达体内不会立即传播,而是在伤口周围的肌肉组织进行复制,随后才会进入外周神经系统并通过神经元逆轴突转运,当到达背根神经节后即开始大量增殖并入侵中枢神经系统。之后病毒便开始离心性传播。因此,RABV在中枢神经系统逃逸神经免疫是引起发病的重要原因,而目前RABV在中枢神经系统逃逸神经免疫的机制尚不清楚。中枢神经系统中的固有细胞以神经元和胶质细胞为主。其中小胶质细胞是中枢神经系统中的免疫细胞,也是其内最主要的吞噬细胞,时刻监视着周围的微环境,而星形胶质细胞在哺乳动物脑中分布最广,因此我们把胶质细胞作为研究对象,开展了不同RABV毒株对胶质细胞功能影响的研究。我们以0.01 MOI剂量的RABV固定毒株B2C、野毒株AH08和SX15感染原代培养的混合胶质细胞,检测了不同病毒在混合胶质细胞中病毒量随时间的变化、不同病毒与溶酶体的共定位及对溶酶体功能的影响、不同病毒对小胶质细胞的活化、分型及与神经元的互作分子的影响。结果显示,RABV固定毒B2C株随着感染时间的增加,病毒量先增加后减少,而野毒株AH08病毒量并没有减少;固定毒B2C株能够定位到溶酶体中,而野毒株AH08并没有与溶酶体共定位;与野毒株AH08和SX15相比,固定毒B2C株能够明显的活化小胶质细胞并刺激小胶质细胞向抗炎性的小胶质细胞分化;野毒株AH08和SX15能够刺激小胶质细胞与神经元互作的抑制性分子CD172α、CD200R和CX3CR1的表达。总之,通过研究RABV与胶质细胞之间的作用,初步探索了部分RABV逃逸机体神经系统免疫反应的机制,为RABV的致病机理研究奠定理论基础,进而为狂犬病的防控以及其它狂犬病毒属病毒的神经免疫逃逸机理研究提供理论依据。
[Abstract]:Rabies (Rabies) is a kind of high mortality zoonosis caused by Rabies virus, which can cause inflammation in the brain of human and other mammals. At present, human rabies cases are mainly transmitted by bitten dogs carrying the virus. RABV does not spread immediately in the body. Instead, it replicates in the muscle tissue around the wound, and then it enters the peripheral nervous system and is transported through neurons against the axon. When the dorsal root ganglion is reached, it begins to proliferate and invade the central nervous system. The virus then begins to spread centrifugally. The immune mechanism of RABV in central nervous system is still unclear. The intrinsic cells in the central nervous system are mainly neurons and glial cells. Microglia are immune cells in the central nervous system and the most important phagocytes in the central nervous system, monitoring the surrounding microenvironment at all times, while astrocytes are the most widely distributed in the mammalian brain. Therefore, we studied the effects of different RABV strains on glial function. We immobilized the virus strain B2C with the dose of 0.01 MOI RABV, and infected the mixed glial cells with AH08 and SX15 in primary culture. We detected the changes of virus amount in the mixed glial cells with different viruses over time. The co-localization of different viruses with lysosomes and the effects of different viruses on lysosome function, the activation, typing and interaction with neurons of microglia by different viruses. The results showed that with the increase of infection time, the amount of AH08 virus increased first and then decreased, but the amount of AH08 virus did not decrease, the fixed strain B2C could locate in lysosome, but the wild strain AH08 did not co-locate with lysosome. Compared with wild virus strains AH08 and SX15, immobilized B2C strain could activate microglia and stimulate the differentiation of microglia into anti-inflammatory microglia. Wild strain AH08 and SX15 could stimulate the expression of CD172 伪 -CD200R and CX3CR1, which interacted between microglia and neurons. In conclusion, by studying the interaction between RABV and glial cells, the mechanism of immune response of part of RABV to escape nervous system was preliminarily explored, which laid a theoretical foundation for the study of pathogenesis of RABV. It provides a theoretical basis for the prevention and control of rabies and the study of neuroimmune escape mechanism of other rabies viruses.
【学位授予单位】：华中农业大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：S852.65
本文编号：2183776
[Abstract]:Rabies (Rabies) is a kind of high mortality zoonosis caused by Rabies virus, which can cause inflammation in the brain of human and other mammals. At present, human rabies cases are mainly transmitted by bitten dogs carrying the virus. RABV does not spread immediately in the body. Instead, it replicates in the muscle tissue around the wound, and then it enters the peripheral nervous system and is transported through neurons against the axon. When the dorsal root ganglion is reached, it begins to proliferate and invade the central nervous system. The virus then begins to spread centrifugally. The immune mechanism of RABV in central nervous system is still unclear. The intrinsic cells in the central nervous system are mainly neurons and glial cells. Microglia are immune cells in the central nervous system and the most important phagocytes in the central nervous system, monitoring the surrounding microenvironment at all times, while astrocytes are the most widely distributed in the mammalian brain. Therefore, we studied the effects of different RABV strains on glial function. We immobilized the virus strain B2C with the dose of 0.01 MOI RABV, and infected the mixed glial cells with AH08 and SX15 in primary culture. We detected the changes of virus amount in the mixed glial cells with different viruses over time. The co-localization of different viruses with lysosomes and the effects of different viruses on lysosome function, the activation, typing and interaction with neurons of microglia by different viruses. The results showed that with the increase of infection time, the amount of AH08 virus increased first and then decreased, but the amount of AH08 virus did not decrease, the fixed strain B2C could locate in lysosome, but the wild strain AH08 did not co-locate with lysosome. Compared with wild virus strains AH08 and SX15, immobilized B2C strain could activate microglia and stimulate the differentiation of microglia into anti-inflammatory microglia. Wild strain AH08 and SX15 could stimulate the expression of CD172 伪 -CD200R and CX3CR1, which interacted between microglia and neurons. In conclusion, by studying the interaction between RABV and glial cells, the mechanism of immune response of part of RABV to escape nervous system was preliminarily explored, which laid a theoretical foundation for the study of pathogenesis of RABV. It provides a theoretical basis for the prevention and control of rabies and the study of neuroimmune escape mechanism of other rabies viruses.
【学位授予单位】：华中农业大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：S852.65
【参考文献】
相关期刊论文 前1条
1 种世桂;赵玉敏;;人狂犬病病例的实验室诊断技术及应用原则[J];甘肃科技;2016年11期
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