Division of Animal Infectious Diseases, State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
PLoS One. 2013;8(2):e55838. doi: 10.1371/journal.pone.0055838. Epub 2013 Feb 7.
Porcine reproductive and respiratory syndrome virus (PRRSV) is an Arterivirus that has been devastating the swine industry worldwide since the late 1980s. To investigate the impact of cellular microRNAs (miRNAs) on the replication of PRRSV, we screened 10 highly conserved miRNAs implicated in innate immunity or antiviral function and identified miR-125b as an inhibitor of PRRSV replication. Virus titer and western blot assays demonstrated that miR-125b reduced PRRSV replication and viral gene expression in a dose-dependent manner in both MARC-145 cell line and primary porcine alveolar macrophages. Mechanistically, miR-125b did not target the PRRSV genome. Rather, it inhibited activation of NF-κB, which we found to be required for PRRSV replication. PRRSV, in turn, down-regulated miR-125b expression post-infection to promote viral replication. Collectively, miR-125b is an antiviral host factor against PRRSV, but it is subject to manipulation by PRRSV. Our study reveals an example of manipulation of a cellular miRNA by an arterivirus to re-orchestrate host gene expression for viral propagation and sheds new light on targeting host factors to develop effective control measures for PRRS.
猪繁殖与呼吸综合征病毒（PRRSV）是一种动脉炎病毒，自 20 世纪 80 年代末以来一直在全球范围内对养猪业造成严重破坏。为了研究细胞 microRNAs（miRNAs）对 PRRSV 复制的影响，我们筛选了 10 种与先天免疫或抗病毒功能相关的高度保守的 miRNAs，并鉴定出 miR-125b 是 PRRSV 复制的抑制剂。病毒滴度和 Western blot 分析表明，miR-125b 以剂量依赖的方式降低了 MARC-145 细胞系和原代猪肺泡巨噬细胞中 PRRSV 的复制和病毒基因表达。从机制上讲，miR-125b 不是靶向 PRRSV 基因组。相反，它抑制了 NF-κB 的激活，而我们发现 NF-κB 是 PRRSV 复制所必需的。反过来，PRRSV 在感染后下调 miR-125b 的表达以促进病毒复制。总之，miR-125b 是一种针对 PRRSV 的抗病毒宿主因子，但它易受 PRRSV 的操纵。我们的研究揭示了动脉炎病毒操纵细胞 miRNA 以重新协调宿主基因表达以促进病毒传播的一个例子，并为针对宿主因子以开发有效的 PRRS 控制措施提供了新的思路。
