小分子热休克蛋白HSP27调节猪繁殖与呼吸综合征病毒引起的炎性反应机制

Compared with low pathogenic strains, HP-PRRSV can induce higher levels of inflammatory factors. This is an important reason for its high pathogenicity. Studies have found that HP-PRRSV can up-regulate the expression of HSP27, while low pathogenic strains can down-regulate the expression of HSP27, suggesting that HSP27 may participate in the regulation of inflammatory response during PRRSV infection. HSP27 can regulate MAPKs and NF-κB-related inflammatory signaling pathways in different cell lines and virus infection processes, but its role in PRRSV infection is not clear. This project aims to study the regulation of HSP27 on inflammatory response in PRRSV infection and its molecular mechanism. HP-PRRSV strain was selected to verify that HP-PRRSV infection can up-regulate the expression of HSP27, then the relationship between HSP27 and HP-PRRSV replication was clarified. We will further to explore the effect of HSP27 on inflammatory factors during PRRSV infection, and study the signaling pathway. Finally, we will study whether the phosphorylation of HSP27 is necessary for its regulation role. This project will provide further understanding of the mechanism of inflammatory response caused by PRRSV, and also provide a new direction for the prevention and control of PRRS.

HP-PRRSV与低致病性毒株相比，可以诱导更高水平的炎性因子，这是其致病性较高的重要原因。研究发现HP-PRRSV可以上调HSP27表达，低致病性毒株下调HSP27表达，因此HSP27可能参与调控PRRSV感染过程中的炎性反应。HSP27可以调控不同细胞及病毒感染过程MAPKs及NF-κB相关炎性信号通路，但其在PRRSV感染中的作用还不明确。本项目旨在研究HSP27在PRRSV感染过程中，对炎性反应的调控作用，并探究其分子机制。选用HP-PRRSV毒株为研究对象，验证了HP-PRRSV感染可以上调HSP27表达，随即明确了HSP27与HP-PRRSV复制的关系。进一步探究在PRRSV感染中，HSP27对炎性因子产生的影响，并深入研究其作用的信号通路。最后，探究HSP27发挥调节作用是否需要其磷酸化。本研究将进一步丰富PRRSV引起的炎症反应机制，同时为防控该病提供新的方向。

热休克蛋白27 (HSP27)属于小热休克蛋白家族，是一种多功能蛋白质。研究表明，HSP27作为一种细胞伴侣，在多种病毒复制过程中发挥重要作用，但其在猪繁殖与呼吸综合征病毒(PRRSV)感染中的作用尚不明确。本研究发现PRRSV感染MARC-145及原代肺泡巨噬细胞(PAMs)可以上调HSP27的表达及磷酸化水平。进一步研究表明，过表达HSP27可以促进PRRSV增殖，而干扰HSP27表达则会抑制PRRSV增殖。抑制HSP27磷酸化，PRRSV增殖水平降低，且病毒双链RNA (dsRNA)水平也降低，而dsRNA是病毒复制和转录复合物(RTC)的标志。此外，HSP27可与多种非结构蛋白相互作用，包括nsp1α、nsp1β、nsp5、nsp9、nsp11和nsp12。抑制HSP27磷酸化几乎完全破坏了它与nsp1β和nsp12的相互作用。综上所述，我们的研究结果揭示了HSP27在PRRSV复制中发挥重要作用，并为通过靶向HSP27对抗PRRSV感染提供了依据。