结核分枝杆菌的持续感染机制不清是严重制约结核病有效防控和治疗的重要因素。在前期工作中，我们验证了结核分枝杆菌分泌蛋白RV3802C特殊的亚细胞定位，分析RV3802C蛋白存在PE-PPE同源区；结合分泌蛋白RV3802C参与构成结核分枝杆菌细胞壁，推测该蛋白与结核分枝杆菌的持留感染密切相关。本项目以结核分枝杆菌分泌蛋白RV3802C为研究对象，在确定其亚细胞定位基序的基础上，构建稳定表达该基因的细胞株，分析稳定表达细胞株与亲本细胞株的转录组差别、NF-kB信号通路及NO含量等的变化；研究与RV3802C蛋白互作的宿主蛋白及其特性；构建结核分枝杆菌H37Rv的基因缺失突变株，分析与持续感染相关的基因转录水平变化；应用豚鼠模型评价突变株和亲本株在感染后不同时间的组织荷菌量、豚鼠存活时间和组织病理学变化。综合以上研究，阐明分泌蛋白RV3802C在结核分枝杆菌持续感染中的作用机制。

Today, the persistent infection mechanism of Mycobacterium tuberculosis is unclear, which is seriously hampered the effective prevention and control and treatment of the tuberculosis. In the previous study, we verified the function of Mycobacterium tuberculosis secreted protein RV3802C sub-cellular localization and analyzed it had PE-PPE homologous region (119-306aa) . Combinative secreted protein RV3802C constitutes the cell wall composition of Mycobacterium tuberculosis, suggesting that the protein has the function of holding the stay Mycobacterium tuberculosis latent infection is closely related. This project will study the secreted protein RV3802C of M. tuberculosis，which is based on the motif determine RV3802C sub-cellular localization. And then we will establish stable cell line for RV3802C's stable expression and analyze the transcriptome difference between stably expressing cell line and parental cell line. We need to analyze the changes of the NF-kB signaling pathway and in the levels of NO. We also need to study the special host protein which could interact with RV3802C protein and their characteristics. Construction of M. tuberculosis H37Rv gene mutant MT△ RV3802C and analyze the changes of gene transcriptome which is related to persistent infection. At last we will utilize guinea pig model to evaluate the changes of tissues biomass, the guinea pig survival time and histopathological changes between mutant and parental strain different time after infection. Based on the above study, the mechanism of secreted proteins RV3802C in persistent infection of Mycobacterium tuberculosis will be elucidated.