狂犬病病毒逆轴浆传输的机制研究

尽管狂犬病危害严重，但目前狂犬病病毒（RABV）逆轴浆传输的机制尚不明确。本项目前期研究发现，RABV感染可使stmn1 、kif5b、klc1、 APC和katn等与骨架相关蛋白的表达水平发生改变，国外研究者发现P蛋白第139-174位氨基酸与动力轻链8（DLC8）存在相互作用，而P蛋白上缺乏此区域的重组RABV仍可侵入中枢神经系统，且囊泡运输为细胞生命活动的基本方式。据此本项目提出如下科学假设：RABV可能在感染的神经细胞内以囊泡形式，借助细胞骨架而实现逆轴浆传输。为此本项目拟通过确定感染的神经细胞内传输RABV的主要囊泡类型、运载此类囊泡的马达蛋白和细胞骨架类型、囊泡表面标志分子及马达蛋白分子的调控表达、骨架的特异性抑制等手段对以上假设加以证实。本项目的成功实施不仅有利于揭示RABV致病机制，其中所阐释的囊泡沿骨架运输的机制对于其他神经感染性病原的研究也具有广泛的指示意义。

Rabies is still seriously endemic in most parts of the world which is causing deaths in large numbers.Various studies have been done to investigate the exact mechanism of pathogenesis of rabies virus, but the retrograde axonal transport mechanism associated rabies virus (RABV) is not well elucidated. Our previous research work revealed that RABV infection differentiated expression of some cytoskeleton proteins, such as stmn1、kif5b、klc1APC、katna1、mylk、gelsolin and Gsk3β.Tan GS et al demonstrated that the 139-174 residues of P protein could interact with dynein light chain 8(DLC8),and the recombinant RABV deleted binding regions on P still invaded the central nervous system. Accordingly, the scientific hypothesis of our project is as follows: RABV probably exists in the vesicles of infected neurons, retrograde axonal transport might be achieved by cytoskeletal motors.This hypothesis will be explored by defining the type of vesicles containing RABV,the motors and cytoskeleton,following with regulated expression or antagonists about vesicle markers and motor proteins. This project could not only helpful to reveal the pathogenesis of RABV, but also help to reveal the mechanism involved in the transport of vesicles along the cytoskeleton. Moreover, it will aid researchers to explore a wide range of other neurological agents in the field of neurology.