pORF5通过lncRNA-ZFAS1调控Wnt/β-catenin信号通路介导沙眼衣原体持续性感染机制研究

沙眼衣原体（Ct）可通过产生效应蛋白介导其持续性感染，但机制不明。pORF5是申请者首次证实由Ct质粒基因编码的分泌性效应蛋白，前期研究发现pORF5可上调宿主锌指结构反义转录本1（lncRNA-ZFAS1），沉默lncRNA-ZFAS1表达后，Ct发育周期受阻，感染力降低；对lncRNA-ZFAS1共表达基因进行KEGG通路注释，发现差异基因显著富集于Wnt/β-catenin通路。据此本项目提出“pORF5通过lncRNA-ZFAS1调控Wnt/β-catenin通路介导Ct持续性感染”的假设。本研究拟采用RNAi等技术建立lncRNA-ZFAS1/Wnt/β-catenin通路关键分子的细胞转染模型以及Ct生殖道感染动物模型，筛选并鉴定该通路关键靶蛋白并揭示其功能，揭示Ct与宿主细胞互作调控机理及其对Ct持续性感染的影响及机制。研究结果将丰富对Ct致病机制的认识，为其防治提供新靶标。

Chlamydia trachomatis (Ct) can establish persistent infection mediated by effector proteins, but the mechanism is still unknown. Our previous work demonstrated that pORF5 encoded by chlamydial plasmid was a secreted effector protein for the first time. Further study showed that pORF5 could increase the expression of lncRNA-ZFAS1, silencing lncRNA-ZFAS1 blocked Ct developmental cycle and decreased Chlamydial infectivity. After the KEGG functional annotation and enrichment analysis for differentially genes co-expressed with lncRNA-ZFAS1, we found that the differentially expressed genes were significantly enriched in the Wnt/β-catenin pathway. Based on these characteristics, we hypothesize that pORF5 protein mediates Ct persistent infection through Wnt/β-catenin signal pathway regulated by lncRNA-ZFAS1.Therefore, the cell transfection model and animal model of Ct genital tract infection were established by using RNAi and gene transfection to screen and identify the key target proteins and their functions related to lncRNA-ZFAS1/Wnt/β-catenin pathway. This work will reveal the mechanisms of interaction between Ct and host cells and its effect on Ct persistent infection. which not only enriches the understanding of Ct pathogenesis, but also provides a new target for its prevention and treatment.