MCPIP1调控猪繁殖与呼吸综合征病毒感染的作用机制研究

Porcine reproductive and respiratory syndrome virus (PRRSV) causes reproductive failure in sows and respiratory distress in piglets, which causes a seriously economic loss in the global swine industry. MCP-1-induced protein-1 (MCPIP1) is a CCCH type zinc-finger-containing protein that acts as a critical immune regulater. MCPIP1 can act as an RNase to promote the mRNA degradation of some inflammatory cytokines. Besides, MCPIP1 can regulate the JNK and NF-κB signaling pathway through deubiquitinating TNF receptor-associated factor family proteins. MCPIP1 also has broad-spectrum antiviral effects by directly targeting viral RNA. Previous study showed that the expression of MCPIP1was upregulated in the anti-PRRSV progress mediated by TLR7 signaling pathway. Moreover, PRRSV infection induced inflammatory cytokines expression as well as MCPIP1. Besides, PRRSV can regulate the JNK and NF-κB signaling pathway to facilitate itself replication. These results indicated that MCPIP1 palys an important role in the host response against PRRSV infection. The purpose of this project is to research the effect of MCPIP1 on PRRSV replication and inflammatory cytokines expression, identification of MCPIP1 targeted proteins, screening of microRNA targeting MCPIP1 and identification of the key domain of MCPIP1, expecting to understand the immune regulation effects of MCPIP1 on PRRSV infection, which will provide new theoretical foundation for the prevention of PRRSV.

猪繁殖与呼吸综合征病毒（PRRSV）感染所致的母猪繁殖与仔猪呼吸障碍给全球养猪业造成了巨大经济损失。MCPIP1是具有RNA酶和去泛素化酶活性的免疫调节型锌指蛋白分子，能靶向降解炎性因子的mRNA、以TRAFs为底物调控JNK和NF-κB等信号通路、直接靶向病毒RNA而实现抗病毒。研究显示，TLR7介导的抗PRRSV过程中MCPIP1表达上调，PRRSV感染PAM后诱导MCPIP1及炎性因子表达，PRRSV能调控JNK和NF-κB等信号通路促进自身增殖。提示MCPIP1在宿主对PRRSV的感染调控中发挥重要作用。本项目拟对MCPIP1调控PRRSV增殖及炎性因子的表达、MCPIP1作用靶蛋白的鉴定、靶向MCPIP1的microRNA的筛选和MCPIP1关键功能域的确定等方面进行研究，期待明确MCPIP1在PRRSV感染过程中发挥免疫调节作用的分子细节，为PRRSV的防控提供新的理论依据。

猪繁殖与呼吸综合征病毒（Porcine reproductive and respiratory syndrome virus, PRRSV）感染所致的母猪繁殖障碍与仔猪呼吸障碍给全球养猪业造成了巨大经济损失。目前尚无完全有效的疫苗或其他防控措施。因此，亟需开发针对PRRSV防治的新靶点和新策略。MCPIP1是一类具有免疫调节作用的CCCH型锌指家族分子，其对PRRSV感染的调控作用及分子机制目前仍不清楚。基于此，本研究首先探讨了PRRSV感染过程中MCPIP1表达的动力学特征。结果表明，PRRSV感染显著上调Marc-145及猪肺泡巨噬细胞中MCPIP1 mRNA和蛋白表达，并且PRRSV ORF7对MCPIP1的上调表达发挥关键作用。然后通过敲低及过表达MCPIP1分析其对PRRSV感染及复制的影响。结果表明，过表达MCPIP1能够促进PRRSV的感染，而敲低或者敲除MCPIP1能够抑制PRRSV感染，且MCPIP1主要影响PRRSV生命周期的复制及组装阶段。对MCPIP1促进PRRSV复制的分子机制的初步研究表明，MCPIP1可能通过诱导胞内脂滴减少影响PRRSV复制。上述研究结果表明，MCPIP1是一种能够促进PRRSV复制的宿主因子，对其促进PRRSV复制的分子机制的深入研究有助于我们深入了解PRRSV-宿主细胞互作网络，并为开发新的PRRSV防控靶点和措施提供了有益的借鉴。