猪肺炎支原体和PRRSV共感染激活IL-1β的分子机制及其生物学意义

猪呼吸道疾病综合症是危害全球养猪业生产最重要的疾病之一，其病原非常复杂，其中猪肺炎支原体（Mhp）和猪繁殖与呼吸综合征病毒（PRRSV）被认为是该病最主要的病原。研究证明这两种病原之间存在相互作用和协同致病，但是其协同致病的分子机制尚不清楚。在青年基金资助下，我们揭示了混合感染后宿主基因表达谱的变化，发现了以炎症因子IL-1β为中心的共感染互作网络，明确了IL-1β是Mhp和PRRSV协同致病的关键因子。本项目拟进一步开展IL-1β在Mhp和PRRSV协同致病中的作用与机制研究，比较单独感染和共感染激活IL-1β信号通路的异同，挖掘参与IL-1β激活的Mhp和PRRSV编码蛋白，解析两者在分子水平上互作的机制，揭示IL-1β产生对PRRSV增殖、Mhp黏附及炎症因子表达的影响，阐明IL-1β在两者共感染中的生物学意义，为有效预防和控制Mhp和PRRSV混合感染的发生与流行提供科学依据。

Porcine respiratory disease complex (PRDC) is one of the most economically important diseases of the global swine industry. Mycoplasma hyopneumoniae (Mhp) and porcine reproductive and respiratory syndrome virus (PRRSV) are two of the most common pathogens isolated from pigs exhibiting PRDC. The previously studies indicated that there were the interaction and synergism between these two pathogens. However, the molecular mechanism of pathogenesis was not yet clear. In the youth fund of National Nature Science Foundation of China, our study showed the changes of the host gene expression profile after co-infections of Mhp and PRRSV, and found the inflammatory factor IL-1β in the center of co-infection interaction network. It revealed that the IL-1β is a key factor of collaborative pathogenic in co-infections of Mhp and PRRSV. In this project, we will research the role and mechanism of IL-1β in the co-infection of Mhp and PRRSV, include (i) the signal pathway of activate IL-1β in the single infection and co-infection; (ii) identify the Mhp and PRRSV proteins responsible for IL-1β activation; (iii) explain the interaction mechanisms of Mhp and PRRSV at the molecular level; (iiii)determine the impact of activate IL-1β on PRRSV proliferation, Mhp adhesion and inflammatory factor expression. The study will reveal the biology significance of IL-1β in the co-infection of Mhp and PRRSV. The new knowledge gained will provide the scientific basis for effective prevention and control.