猪胸膜肺炎放线杆菌（APP）是引起猪胸膜肺炎的病原菌，APP感染常造成大量猪死亡，给全球养猪业造成了巨大的经济损失。APP可分泌4种外毒素即ApxIA、ApxIIA、ApxIIIA和ApxIVA，但只有ApxIVA存在于所有15个血清型APP中，而且ApxIVA只能在APP感染动物的体内环境条件下才能获得表达。尽管Apx外毒素是APP的主要致病毒力因子，但国内外研究者对Apx外毒素特别是ApxIVA在APP感染过程中的分子致病机制仍不清楚。因此，本项目拟以ApxIVA和猪肺上皮细胞系为研究对象，采用转录组分析、酵母双杂交和双分子荧光互补等技术，开展ApxIVA对细胞生长、基因表达的影响及蛋白质互作的研究， 阐明ApxIVA对靶细胞基因差异表达的调控作用，揭示ApxIVA的细胞表面受体和相关蛋白互作网络，解析靶细胞内与ApxIVA相关的信号转导通路，达到阐明ApxIVA分子致病机制的目的。

Actinobacillus pleuropneumoniae (A. pleuropneumoniae) is the causative agent of porcine pleuropneumoniae,which causes swine massive death and is responsible for large economic losses in pig industry worldwide. A. pleuropneumoniae can secrete different combinations of four exotoxins (ApxIA, ApxIIA, ApxIIIA, and ApxIVA) belonging to the RTX toxin family. ApxIVA has been demonstrated to present in all 15 serovars of A. pleuropneumoniae, however, it is only expressed under in vivo conditions. Apx exotoxins are important pathogenic virulence factors of A. pleuropneumoniae, but the molecular pathogenic mechanisms of Apx exotoxins, especially ApxIVA during A. pleuropneumoniae infection remain unclear. So this project will focus on research on the effect of ApxIVA on cell growth, gene expression and protein interaction in the porcine lung epithelial cell line（SJPL） by transcriptome analysis (RNA-Seq), yeast two-hybrid, bimolecular fluorescence complementation (BiFC) and so on. This research will elucidate the effect of ApxIVA on gene differential expression of the cells; reveal the cell receptor of ApxIVA and the protein interaction in the cells. The research results will show the signal transduction pathways in the porcine lung epithelial cells stimulated by ApxIVA, and illustrate the molecular pathogenic mechanisms of ApxIVA finally.