Cellular microRNA bta-miR-222 suppresses caprine parainfluenza virus type 3 replication via downregulation of interferon regulatory factor 2
Cellular microRNA bta-miR-222 suppresses caprine parainfluenza virus type 3 replication via downregulation of interferon regulatory factor 2
复制标题
细胞 microRNA bta-miR-222 通过下调干扰素调节因子 2 抑制山羊副流感病毒 3 型复制
DOI：
10.1016/j.vetmic.2018.08.028
复制
发表时间：
2018-10-01
影响因子：
3.3
通讯作者：
Liu, Maojun
中科院分区：
文献类型：
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作者：
Li, Jizong;Mao, Li;Liu, Maojun
山羊副流感病毒3型（CPIV3）是山羊行业重要的呼吸道病原体，2014年在中国发现。大量研究表明，microRNAs （miRNAs）在病毒感染中起着关键作用，但miRNAs在CPIV3感染中的作用尚不清楚。在这项研究中，我们通过深度测序发现，与未感染的MDBK细胞相比，感染CPIV3菌株JS2013的MadinDarby牛肾（MDBK）细胞中，包括bta-miR-222在内的一组mirna显著下调。过表达bta-miR-222可显著降低体外CPIV3的复制，而抑制内源性bta-miR-222可增强CPIV3的复制。Bta-miR-222在MDBK细胞中增强I型干扰素表达并抑制CPIV3复制。此外，我们通过荧光素酶报告基因检测表明，bta-miR-222直接靶向干扰素调节因子2 （IRF2）的3'-非翻译区。用btamiR-222模拟物转染细胞导致IRF2 mRNA和蛋白水平下降，从而导致I型干扰素水平增加和抗病毒反应增强。总之，这些数据证明了bta-miR-222在限制CPIV3复制中的重要作用，并提出了针对CPIV3的潜在抗病毒策略。
Caprine parainfluenza virus type 3 (CPIV3) is an important respiratory pathogen in the goat industry and was detected in China in 2014. Numerous studies have shown that microRNAs (miRNAs) play critical roles in viral infections, but the involvement of miRNAs during CPIV3 infection is poorly understood. In this study, we showed by deep sequencing that a panel of miRNAs, including bta-miR-222, were significantly downregulated in MadinDarby bovine kidney (MDBK) cells infected with CPIV3 strain JS2013 compared with uninfected MDBK cells. Overexpression of bta-miR-222 significantly reduced CPIV3 replication in vitro, while inhibition of endogenous bta-miR-222 enhanced CPIV3 replication. Bta-miR-222 enhanced type I interferon expression and suppressed CPIV3 replication in MDBK cells. Moreover, we showed using luciferase reporter assays that bta-miR-222 directly targeted the 3'-untranslated region of interferon regulatory factor 2 (IRF2). Transfection of cells with btamiR-222 mimics resulted in decreased IRF2 mRNA and protein levels, with a consequent increase in type I interferon levels and potentiation of antiviral responses. Together, these data demonstrate the important role of bta-miR-222 in restricting CPIV3 replication and suggest potential antiviral strategies against CPIV3.