microRNAs调控猪繁殖与呼吸综合征病毒感染和细胞嗜性的分子机制研究

猪繁殖与呼吸综合征病毒（PRRSV）流行给我国养猪业造成巨大经济损失。PRRSV有严格的细胞嗜性，主要感染单核巨噬细胞，特别是猪肺泡巨噬细胞和组织中的巨噬细胞，然而骨髓细胞、外周血单核细胞和腹腔巨噬细胞却不易被感染。目前，我们仍不清楚PRRSV感染和细胞嗜性的分子基础。最近研究表明，宿主microRNAs（miRNAs）作为调节性小RNA可广泛参与病毒感染过程。本项目拟从miRNAs着手，分析感染性不同的巨噬细胞中miRNAs表达差异；筛选和验证具有调节PRRSV复制、细胞抗病毒反应以及调节PRRSV受体CD163的miRNAs；鉴定miRNAs调控PRRSV感染细胞嗜性的靶基因，进而阐明miRNAs调控PRRSV感染和细胞嗜性的分子机制。研究结果将为进一步明晰PRRSV感染机制和致病机理提供重要线索，为开发新型疫苗和抗PRRSV药物提供理论基础和指导。

Porcine reproductive and respiratory syndrome (PRRS) is caused by PRRS virus (PRRSV), leading to significant economic losses. The virus has a very restricted tropism for cells of the macrophage-monocytic lineage. However, the bone marrow monocytes, blood monocytes, and peritoneal macrophage are resistant to PRRSV infection. Until now, it is not clear about the underlying mechanisms for PRRSV to infect macrophages. Recent reports have been showing that host microRNAs (miRNAs) as regulatory small RNAs are widely involved in viral infection. In this proposal, we are going to investigate how miRNAs participate in PRRSV infection. To answer this question, we will analyze the profiles of miRNAs in less permissive cells (blood monocytes and peritoneal macrophage) and permissive alveolar macrophages. Subsequently, we will study how miRNAs in different cells directly or indirectly regulate PRRSV replication, anti-viral activity, and PRRSV receptor CD163 to determine cell tropism, Particularly，we will identify and investigate those genes targeted by miRNAs to regulate PRRSV infection. This project will help us further understand the mechanism of PRRSV infection and pathogenesis, and provide fundamental basis for developing new vaccines and strategies to control PRRSV.