狂犬病病毒感染潜伏期机体免疫应答的分子机制研究

项目名称： 狂犬病病毒感染潜伏期机体免疫应答的分子机制研究

项目编号： No.31472176

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 水产学、兽医学

项目作者： 张守峰

作者单位： 中国人民解放军军事科学院军事医学研究院

项目金额： 82万元

中文摘要： 狂犬病病毒（RABV）具有嗜神经性，在其进入中枢神经系统形成不可逆感染之前，需经历数日至数年的潜伏期。研究表明，RABV强毒在潜伏期内并不刺激机体产生明显的保护性免疫应答，而弱毒可刺激机体产生较高水平的中和抗体，导致其不能形成致死性感染。阐明上述免疫应答差异的分子机制是揭示RABV感染过程的基础，也是从分子水平阻断感染和治疗疾病的理论前提。本实验室对RABV强弱毒株感染的免疫应答规律、RABV感染后中枢神经系统蛋白表达及潜伏期血清蛋白表达差异进行了前期研究，积累了大量数据。本研究拟在前期研究基础上，以不同毒力的RABV感染小鼠及犬，对潜伏期外周及中枢的免疫细胞、免疫因子及蛋白质组进行定量分析，对比不同病毒感染后3周内固有免疫及适应性免疫应答相关标志物的变化特点，解析其变化规律，进而阐明RABV感染潜伏期机体免疫应答差异的分子机制，为狂犬病感染机制的阐明和早期诊断及救治奠定理论基础。

中文关键词： 狂犬病病毒；分子机制；病毒感染；免疫应答

英文摘要： Rabies virus (RABV) is neurotropic and an incubation period of several days to years exists before the viruses reach the central nervous system and form an irreversible infection. Research showed that RABV virulent isolates did not stimulate protective immune response obviously while the attenuated ones could stimulate the body to produce higher level neutralizing antibodies which cause it could not form a lethal infection. Clarifying the molecular mechanism of the immune response differences is the basis of revealing RABV infection process and the theory premise of blocking infection and treating rabies. In author's laboratory, the preliminary studies have been performed about the immune response regularity, tissue protein and serum protein expression differences after virulent and attenuated RABV isolates infection. In this study, based on the previous research, some different virulent RABVs will be infected mice and dogs, and in the incubation period, the peripheral and central immune cells, the immune factors and immune-associated proteins will be analysis quantitatively. The change regular and characteristic of inherent and adaptive immune-associated markers will be analyzed and compared in order to clarify the molecular mechanism of the body's immune response differences and establish the theoretical basis for rabies early diagnosis and treatment.

英文关键词： rabies virus;molecular mechanism;virus infection;immune response