我国不同黑热病流行区利什曼原虫致病差异分子基础的研究

Visceral leishmaniasis (kala-azar) caused by Leishmanias belonging to Leishmania donovani complex is a serious parasitic disease, resulting in significant health problem worldwide. The outcome of leishmania infection depands on parasite virulence, the genetic background and immune response of the host. While the clinical manifestation is determined by infecting parasite. However, limited parasite's molecules relative to clinical manifestation has found, which hinders the understanding of pathological mechanism, development of vaccine and medicine, and establishing of control strategy. Three epidemiological types of visceral leishmaniasis exist in China. All of they caused by leishmania strains belonging to L. donovani complex, presenting similar clinical manifestation, but showing the differences in population affected, latent period and animal host, etc. The molecules relative to these differences are not clear. In this study we plan: (1)to type leishmania strains from three types of visceral leishmaniasis endemic areas based on isoenzymatic Analysis; (2)to understand the molecular basis underlineing the differences in clinical manifestation caused by these leishmania strains based on screening and identification of molecules relative to pathogenicity by quantitative proteomic comparison of these leishmania strains and survey of histopathological changes in model animals caused by infection of leishmania strain with relative gene knocked-out. This study will not only contribute to understand pathogenicity of leishmania, to provide target molecules for development of vaccine and medicine, but also provide theoretic basis for establishing strategy for control visceral leishmaniasis in China.

黑热病是由利什曼原虫感染所致的严重危害人类健康的自然疫源性寄生虫病，在我国是重要的地方病。当前对利什曼原虫致病分子基础认识的局限不仅制约了对致病机理的认识，也妨碍了疫苗和治疗药物的研发。在我国目前存在三种黑热病流行区，它们均是由亲缘关系近的杜氏利什曼原虫复合体内的原虫感染引起，所致疾病的临床表现相似，但在发病人群、潜伏期和宿主等方面存在差异,但导致差异的分子基础未知。本研究首先应用同工酶谱分析法对来自我国不同黑热病流行区利什曼原虫进行分型；二是应用定量蛋白质组学方法比较分析不同流行区来源虫株的前鞭毛体和无鞭毛体蛋白表达谱，筛选差异分子，鉴定并预测其功能；观察应用敲除编码相关分子基因的虫株感染动物引起的病理变化以评价有关分子的病理作用，从而阐明我国不同黑热病流行区利什曼原虫致病差异的分子基础。本研究成功不仅有助于理解利什曼原虫的致病机理，鉴定的分子也为疫苗和治疗药物等的研发提供分子基础。