Cong Peiqing, Xiao Shuqi, Chen Yaosheng, Wang Liangliang, Gao Jintao, Li Ming, He Zuyong, Guo Yunxue, Zhao Guangyin, Zhang Xiaoyu, Chen Luxi, Mo Delin, Liu Xiaohong
State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
Mol Biol Rep. 2014 Sep;41(9):5863-75. doi: 10.1007/s11033-014-3460-7. Epub 2014 Jun 25.
Porcine reproductive and respiratory syndrome (PRRS) is one of the most significant viral diseases in swine, which causes large economic losses to the swine industry worldwide. There is considerable strain variation in PRRSV and two examples of this are the highly virulent Chinese-type PRRSV (H-PRRSV) and the classical North American type PRRSV (N-PRRSV), both with different pathogenesis. These differences may be due in part to genetic and phenotypic differences in virus replication, but also interaction with the host cell. MicroRNAs (miRNAs) are crucial regulators of gene expression and play vital roles in virus and host interactions. However, the regulation role of miRNAs during PRRSV infection has not been systematically investigated. In order to better understand the differential regulation roles of cellular miRNAs in the host response to PRRSV, miRNA expression and a global mRNA transcriptome profile was determined in primary cells infected with either H-PRRSV or N-PRRSV as multiple time points during the viral lifecycle. miRNA-mRNA interactome networks were constructed by integrating the differentially expressed miRNAs and inversely correlated target mRNAs. Using gene ontology and pathway enrichment analyses, cellular pathways associated with deregulated miRNAs were identified, including immune response, phagosome, autophagy, lysosome, autolysis, apoptosis and cell cycle regulation. To our knowledge, this is the first global analysis of strain-specific host miRNA molecular signatures associated with H- and N-PRRSV infection by integrating miRNA and mRNA transcriptomes and provides a new perspective on the contribution of miRNAs to the pathogenesis of PRRSV infection.
猪繁殖与呼吸综合征(PRRS)是猪最重要的病毒性疾病之一,给全球养猪业造成巨大经济损失。PRRS病毒存在相当大的毒株差异,其中两个例子是高致病性中国型PRRS病毒(H-PRRSV)和经典北美型PRRS病毒(N-PRRSV),二者具有不同的发病机制。这些差异可能部分归因于病毒复制过程中的基因和表型差异,也与宿主细胞的相互作用有关。微小RNA(miRNA)是基因表达的关键调节因子,在病毒与宿主的相互作用中发挥着重要作用。然而,miRNA在PRRS病毒感染过程中的调节作用尚未得到系统研究。为了更好地了解细胞miRNA在宿主对PRRS病毒反应中的差异调节作用,在病毒生命周期的多个时间点,对感染H-PRRSV或N-PRRSV的原代细胞进行了miRNA表达和全基因组mRNA转录组分析。通过整合差异表达的miRNA和负相关的靶mRNA构建了miRNA-mRNA相互作用组网络。利用基因本体和通路富集分析,确定了与失调miRNA相关的细胞通路,包括免疫反应、吞噬体、自噬、溶酶体、自溶、凋亡和细胞周期调控。据我们所知,这是首次通过整合miRNA和mRNA转录组对与H-PRRSV和N-PRRSV感染相关的毒株特异性宿主miRNA分子特征进行全面分析,并为miRNA对PRRS病毒感染发病机制的贡献提供了新的视角。