高致病性猪繁殖与呼吸综合征病毒（HP-PRRSV）引起高热的分子机制研究

高致病性猪繁殖与呼吸综合征（无名高热）由高致病性猪繁殖与呼吸综合征病毒（HP-PRRSV）引起，其特点为急性高热、高感染率和高致死率。我们前期研究发现HP-PRRSV可激活ERK信号通路，促进COX-1的转录表达，进而诱导调前列腺素E2 （PGE2）产生。HP-PRRSV上调PGE2可能是引起猪高热的原因之一。在本项目中，我们将进一步研究HP-PRRSV上调PGE2所依赖的信号通路及相关分子机理；确定诱导PGE2上调的HP-PRRSV蛋白及其作用的分子机制；分析高致病性PRRSV与经典PRSSV毒株诱导发热能力不同的分子机理；并根据研究结果对HP-PRRSV进行致弱。本课题成果将进一步揭示HP-PRRSV的致病机理，为开发新型抗PRRSV疫苗提供理论依据。

Porcine reproductive and respiratory syndrome (PRRS) caused by PRRSV is one of the most economically important viral diseases for the swine industry worldwide. PRRSV, in particular, HP-PRRSV, can cause high fever. In our previous study, we found out that HP-PRRSV infection could increase PGE2 production by up-regulation of COX-1. Our results indicate that HP-PPRSV elicits the expression of COX-1 through the ERK1/2-p-C/EBP-signaling pathway, resulting in the increase of PGE2, which plays a critical role in inducing high fever in PRRSV infected pigs. In this study, we are going to further exploit the mechanisms by which HP-PRRSV leads to high fever. We will study which HP-PRRSV protein(s) promotes the PGE2 secretion, and the related molecular mechanism. Moreover, we will study the different abilities of HP-PRRSV and typical PRRSV strains to induce fever. In addition, we will study the correlation between the PGE2 levels and the severity of symptoms caused by PRRSV infection. Finally, we will try to attenuate HP-PRRSV based our results using reverse genetics technique. This work will provide new insights into the molecular mechanisms of HP-PRRSV pathogenesis and new clues for new vaccine strategies against PRRSV.