狂犬病病毒（RABV）街毒株感染是发展中国家引起临床人狂犬病的几乎唯一来源，但目前国内外对其在感染伤口部位是否复制、与其他毒株细胞生物学特性上的差异及犬唾液分泌机制等基本问题尚有待深入。为此，本项目拟通过制备小鼠皮肤、肌肉组织原代细胞，并结合切断坐骨神经小鼠肌肉接种，从核酸、蛋白水平检验其增殖情况,以回答其是否复制问题；然后在感染细胞内检测不同毒株引起包涵体、应激颗粒的动态变化及基因组、反基因组、mRNA及蛋白水平的变化，同时研究G和M蛋白复制所涉的细胞器，结合RABV基因组表观遗传学特征，以期分析RABV街毒株的增殖特性和装配及出芽等细节；对RABV发病犬唾液成分变化、所支配唾液腺的神经类型及脑内核团进行研究，并结合脑核团定位注射，综合分析RABV街毒株诱导唾液分泌的机制。针对以上3个基本问题的深入研究结果，对于指导我国犬源性人狂犬病的防治意义重大。

Street rabies virus (RABV) infection is almost the only source of clinical human rabies in developing countries, but whether it is replicated at the wound site, the differences among the strains in cellular biological characteristics and the mechnisms of canine saliva secretion，all these need to be deepened in the fields of domestic and abroad. . This project intends to prepare primary cells from mouse skin and muscle tissue ,combining with innervated muscle inoculation in sciatic nerve cutting mice , test the proliferation of nucleic acid and protein，try to answer the replication status of the viruses at the wound ; then the dynamics are detected such as size of inclusion bodies and stress granules, genome, antigenome, mRNA and protein levels, even colocalization of G and M proteins with organelles simultaneously . combining with genomic epigenetic features of street RABV, get more precise information about proliferation characteristics and assembly and budding of RABV street strains . . Based on the changes of saliva composition in RABV-infected dogs, the type of nerves in which salivary glands are innervated, and RABV localization injection in brain nucleus, comprehensive analysis of the mechanism about salivary secretion induced by RABV street strain infection. The in-depth study of these basic problems is of great significance for the prevention of canine-derived human rabies and PEP after exposure to rabid dog.