Xiao Shuqi, Wang Xue, Ni Huaibao, Li Na, Zhang Angke, Liu Hongliang, Pu Fengxing, Xu Lele, Gao Jiming, Zhao Qin, Mu Yang, Wang Chengbao, Sun Yani, Du Taofeng, Xu Xingang, Zhang Gaiping, Hiscox Julian A, Goodfellow Ian G, Zhou En-Min
College of Veterinary Medicine, Northwest A&F University, Shaanxi, China Experimental Station of Veterinary Pharmacology and Veterinary Biotechnology, Ministry of Agriculture, China, Shaanxi, China.
College of Veterinary Medicine, Northwest A&F University, Shaanxi, China College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan, China.
J Virol. 2015 Apr;89(8):4494-503. doi: 10.1128/JVI.02810-14. Epub 2015 Feb 4.
Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically important viruses affecting the swine industry worldwide. Our previous research showed that PRRSV downregulates the expression of heme oxygenase-1 (HO-1), a pivotal cytoprotective enzyme, postinfection and that overexpression of HO-1 inhibits PRRSV replication. MicroRNAs regulate gene expression at the posttranscriptional level and have recently been demonstrated to play vital roles in pathogen-host interactions. The present study sought to determine whether microRNAs modulate HO-1 expression and, by doing so, regulate PRRSV replication. Using bioinformatic prediction and experimental verification, we demonstrate that HO-1 expression is regulated by miR-24-3p. A direct interaction between miR-24-3p and HO-1 mRNA was confirmed using a number of approaches. Overexpression of miR-24-3p significantly decreased HO-1 mRNA and protein levels. PRRSV infection induced miR-24-3p expression to facilitate viral replication. The suppressive effect of HO-1 induction by protoporphyrin IX cobalt chloride (CoPP; a classical inducer of HO-1 expression) on PRRSV replication in MARC-145 cells and primary porcine alveolar macrophages could also be reversed by overexpression of miR-24-3p. Collectively, these results suggested that miR-24-3p promotes PRRSV replication through suppression of HO-1 expression, which not only provides new insights into virus-host interactions during PRRSV infection but also suggests potential new antiviral strategies against PRRSV infection.
MicroRNAs (miRNAs) play vital roles in viral infections by regulating the expression of viral or host genes at the posttranscriptional level. Heme oxygenase-1 (HO-1), a pivotal cytoprotective enzyme, has antiviral activity for a number of viruses, such as Ebola virus, hepatitis C virus, human immunodeficiency virus, and our focus, PRRSV, which causes great economic losses each year in the swine industry worldwide. Here, we show that PRRSV infection induces host miRNA miR-24-3p expression and that miR-24-3p regulates HO-1 expression through both mRNA degradation and translation repression. Suppression of HO-1 expression by miR-24-3p facilitates PRRSV replication. This work lends credibility to the hypothesis that an arterivirus can manipulate cellular miRNAs to enhance virus replication by regulating antiviral responses following viral infection. Therefore, our findings provide new insights into the pathogenesis of PRRSV.
猪繁殖与呼吸综合征病毒（PRRSV）是影响全球养猪业的最重要的经济病毒之一。我们之前的研究表明，PRRSV感染后会下调血红素加氧酶-1（HO-1）的表达，HO-1是一种关键的细胞保护酶，并且HO-1的过表达会抑制PRRSV复制。微小RNA在转录后水平调节基因表达，最近已证明其在病原体与宿主相互作用中发挥重要作用。本研究旨在确定微小RNA是否调节HO-1表达，并由此调节PRRSV复制。通过生物信息学预测和实验验证，我们证明HO-1表达受miR-24-3p调节。使用多种方法证实了miR-24-3p与HO-1 mRNA之间存在直接相互作用。miR-24-3p的过表达显著降低了HO-1 mRNA和蛋白质水平。PRRSV感染诱导miR-24-3p表达以促进病毒复制。原卟啉IX氯化钴（CoPP；HO-1表达的经典诱导剂）对MARC-145细胞和原代猪肺泡巨噬细胞中PRRSV复制的诱导HO-1的抑制作用也可被miR-24-3p的过表达逆转。总体而言，这些结果表明miR-24-3p通过抑制HO-1表达促进PRRSV复制，这不仅为PRRSV感染期间的病毒-宿主相互作用提供了新见解，还提示了针对PRRSV感染的潜在新抗病毒策略。
微小RNA（miRNA）通过在转录后水平调节病毒或宿主基因的表达在病毒感染中发挥重要作用。血红素加氧酶-1（HO-1）是一种关键的细胞保护酶，对多种病毒具有抗病毒活性，如埃博拉病毒、丙型肝炎病毒、人类免疫缺陷病毒，以及我们关注的每年在全球养猪业造成巨大经济损失的PRRSV。在这里，我们表明PRRSV感染诱导宿主miRNA miR-24-3p表达，并且miR-24-3p通过mRNA降解和翻译抑制来调节HO-1表达。miR-24-3p对HO-
