血红素加氧酶1抑制猪繁殖与呼吸综合征病毒复制的分子机制

项目名称： 血红素加氧酶1抑制猪繁殖与呼吸综合征病毒复制的分子机制

项目编号： No.31472173

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 水产学、兽医学

项目作者： 肖书奇

作者单位： 西北农林科技大学

项目金额： 83万元

中文摘要： 猪繁殖与呼吸综合征（PRRS）是危害全球养猪业的重大病毒性疫病，但目前对该病的预防和控制尚未取得突破性进展。我们发现血红素加氧酶1（HO-1）显著抑制PRRSV在其易感细胞Marc-145和PK-15CD163及宿主靶细胞PAM中复制。因此推测HO-1也可能抑制该病毒在猪体内复制。HO-1抑制PRRSV复制的分子机制是什么？为了回答这一重要科学问题，本研究首先在猪体内验证HO-1抑制PRRSV复制；然后运用高表达、RNAi、Co-IP、BiFC、FACS和激光共聚焦等方法，通过解析调控HO-1表达进而抑制PRRSV复制的上游关键转录因子、鉴定与HO-1互作的下游PRRSV蛋白并明确二者互作对病毒复制的影响，从宿主基因的转录调控及病毒蛋白与宿主蛋白相互作用的角度深入研究HO-1抑制PRRSV复制的分子机制。为进一步阐明PRRSV的分子致病机制并确立HO-1作为PRRS防治新靶点提供科学依据。

中文关键词： 猪繁殖与呼吸综合征病毒；血红素加氧酶1；抗病毒；分子机制

英文摘要： Porcine reproductive and respiratory syndrome(PRRS) is one of the most economically important swine viral infectious diseases affecting swine industry worldwide. However, current antiviral strategy could not effectively prevent and control this disease. Our recent studies have demonstrated that induction or over-expression of heme oxygenase 1 (HO-1) inhibited PRRS virus (PRRSV) replication in PRRSV permissive cells, Marc-145, PK-15CD163, and primary alveolar macrophages (PAM). Our hypothesis is that HO-1 also inhibit PRRSV replication in pig. What are the molecular mechanisms of HO-1 in the inhibition of PRRSV replication ? To test this hypothesis, firstly, we propose to test the ability of HO-1 to inhibit PRRSV replication in pig. Then we determine the specific transcription factors regulating HO-1 gene expression and PRRSV replication, and define PRRSV proteins interacting with HO-1 and their role during PRRSV infection by employing over-expression, RNA interference (RNAi), Co-Immunoprecipitation (Co-IP), Bimolecular Fluorescence Complementation (BiFC), Confocal colocalization, and other techniques. The proposed studies are expected to provide additional information for better understanting the molecular mechanisms of HO-1 in inhibiting PRRSV replication from the aspects both transcriptional regulation and virus-host interaction. The results generated from this project will pave the way for elucidating the molecular machnisms of PRRSV pathogenesis and developing HO-1 based novel approach for the prevention and control of PRRS.

英文关键词： PRRSV;HO-1;Anti-PRRSV;Molecular mechnisms