MicroRNA-30c targets the interferon-alpha/beta receptor beta chain to promote type 2 PRRSV infection
MicroRNA-30c targets the interferon-alpha/beta receptor beta chain to promote type 2 PRRSV infection
复制标题
DOI：
10.1099/jgv.0.001166
复制
发表时间：
2018-12-01
影响因子：
3.8
通讯作者：
Feng, Wen-hai
中科院分区：
文献类型：
--
作者：
Liu, Fang;Wang, Honglei;Feng, Wen-hai
猪繁殖与呼吸综合征（PRRS）是猪的主要疾病之一。microrna （mirna）已成为病毒与宿主细胞相互作用的重要调节因子，miR-30c已被发现可促进PRRSV的复制。在这里，我们发现干扰素- α / β受体β链（IFNAR2）在HV（一种高致病性的2型PRRSV毒株）和CH-1a（一种经典的2型PRRSV毒株）感染期间下调，而miR-30c上调。随后，通过生物信息学分析，我们预测IFNAR2被miR-30c靶向。荧光素酶测定证实，miR-30c靶向IFNAR2的3' UTR，因为靶序列或miR-30c种子序列的突变逆转了荧光素酶的活性。此外，miR-30c和IFNAR2 mRNA在rna诱导沉默复合体（RISC）中物理共定位。重要的是，我们发现miR-30c也通过靶向IFNAR2破坏了ifn刺激基因（ISGs）的诱导。我们的发现进一步揭示了miR-30c促进PRRSV复制的机制。
Porcine reproductive and respiratory syndrome (PRRS) is one of the most important diseases in pigs. MicroRNAs (miRNAs) have emerged as an important regulator of virus-host cell interactions and miR-30c has been found to facilitate PRRSV replication. Here, we found that the interferon-alpha/beta receptor beta chain (IFNAR2) was down-regulated, while miR-30c was up-regulated during HV (a highly pathogenic type 2 PRRSV strain) and CH-1a (a classic type 2 PRRSV strain) infection. Subsequently, using bioinformatics analysis, we predicted that the IFNAR2 was targeted by miR-30c. A luciferase assay verified that the 3' UTR of IFNAR2 was targeted by miR-30c, as a mutation on either the target sequence or the miR-30c seed sequence reversed the luciferase activity. In addition, miR-30c and IFNAR2 mRNA were physically co-localized in RNA-induced silencing complex (RISC). Importantly, we showed that miR-30c also impaired the induction of IFN-stimulated genes (ISGs) by targeting IFNAR2. Our findings further reveal the mechanism of miR-30c promoting PRRSV replication.