狂犬病病毒弱毒株对不同日龄乳鼠致病性差异机理的研究

项目名称： 狂犬病病毒弱毒株对不同日龄乳鼠致病性差异机理的研究

项目编号： No.31201918

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 畜牧学与草地科学、兽医学、水产学

项目作者： 王晓虎

作者单位： 广东省农业科学院动物卫生研究所

项目金额： 23万元

中文摘要： 狂犬病病毒（RV）弱毒株一般在成年动物不致病，而在初生动物常致病死亡。试验发现，RV弱毒株SRV9即使是致乳鼠死亡，也是在13日龄以下，18日龄以上则不发病；而14～17日龄乳鼠则是部分死亡，且存活的乳鼠在其后的2个月中，生长受到明显抑制。为何SRV9对仅相差数天的乳鼠致病性差异显著？以此为切入点，预实验表明，致死日龄前后乳鼠脑内一些蛋白的差异表达及其信号通路的改变发挥了关键作用,例如CRMP-4蛋白、干扰素和Ras通路。因此，本项目拟对致死日龄前后及攻毒存活的乳鼠，进行细致的蛋白质组学分析；对差异表达蛋白进行生物信息学的功能注释和Pathway分析，筛选出有意义的靶蛋白（CRMP-4等）；进而对靶蛋白及其信号通路上的关键蛋白，进行免疫印迹、基因沉默和过表达等蛋白互作的功能验证。从而确定SRV9致死乳鼠中起关键调控作用的靶蛋白及其调控路径，揭示RV弱毒株对不同日龄乳鼠致病性差异的分子机制。

中文关键词： 狂犬病；弱毒株；病毒感染；蛋白质组学；致病性

英文摘要： In general the attenuated strains of Rabies virus(RV) do not cause the death of adult animals, however it may do in newborn animals. Our experiments find that the attenuated strain, SRV9, can result in the death of the suckling mouse younger than 13 days old, but not in those older than 18 days. And a proportion of animals aged between 14 and 17 days old died too, those who survived had got an adverse effect in their growth and development in the subsequent 2 months, characterized by a slow increase in body weight, being significantly smaller than control. The preliminary experimental results show that the different expression of some proteins in the brain of suckling mouse may play a key regulatory role， for example CRMP-4,IFN,Ras pathway. Therefore, this project intends to have a detailed proteomic analysis to the neonatal rats before and after lethal-day and the neonatal rats survived; analyse the proteins expressed differentially in term of bioinformatics annotation and pathway; screen important target proteins; and functionally verify the target proteins through gene silencing, over expression, immunological coprecipitation and protein-protein interactions. Thereby, we can determine target proteins which play a key role in the regulation of the phenomenon above and their possible regulatory pathways,

英文关键词： Rabies；Attenuated strain；Viral infection；Proteomics；Pathogenic mechanism