Borna disease virus encoded phosphoprotein inhibits host innate immunity by regulating miR-155
Borna disease virus encoded phosphoprotein inhibits host innate immunity by regulating miR-155
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博尔纳病病毒编码的磷蛋白通过调节miR-155抑制宿主先天免疫
DOI：
10.1016/j.antiviral.2013.02.009
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发表时间：
2013-04-01
影响因子：
7.6
通讯作者：
Zhang, Fengmin
中科院分区：
文献类型：
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作者：
Zhai, Aixia;Qian, Jun;Zhang, Fengmin
据报道，博尔纳病病毒（Borna disease virus，BDV）编码的磷蛋白（phosphoprotein，P蛋白）可以抑制Traf家族成员相关的NF-κ B激活剂（TANK）结合激酶1（TBK-1）的活性，从而阻止I型干扰素（IFN）的诱导。然而，microRNA对BDV感染和宿主免疫应答的调节作用尚未被表征。RNAhybrid软件预测miR-155与BDV P mRNA互补。在此，我们发现miR-155在BDV持续感染的人少突胶质细胞（OL/BDV）中下调，并且BDV P蛋白而不是X蛋白直接抑制细胞中miR-155的表达。当miR-155过表达时，BDV对细胞中I型IFN的抑制被逆转，并且I型IFN的表达增加。当特异性阻断miR-155表达时，细胞IFN表达和poly I：C处理对IFN的诱导受到抑制。此外，miR-155通过靶向细胞因子信号转导抑制因子1（SOCS 1）和SOCS 3促进I型IFN的产生。SOCS 3的nt 1138-nt 1158区域的突变放弃了miR-155对SOCS 3增强的绿色荧光蛋白（EGFP）表达的影响。当miR-155过表达时，OL/BDV细胞中BDV P-EGFP的mRNA和蛋白水平显著降低，而miR-155突变不影响BDV P-EGFP的表达。因此，BDV持续感染通过抑制miR-155抑制I型IFN的表达，miR-155在BDV持续感染中发挥重要的免疫调节作用。(c)2013爱思唯尔有限公司版权所有。
It has been reported that the Borna disease virus (BDV) encoded phosphoprotein (P protein) can inhibit the activity of Traf family member-associated NF-kappaB activator (TANK)-binding kinase 1 (TBK-1), thus preventing the induction of type I interferon (IFN). However, the effects of microRNA on the regulation of BDV infection and the host's immune response have not been characterized. miR-155 was predicted to be complementary to the BDV P mRNA by RNAhybrid software. Here, we showed that miR-155 was down-regulated in BDV persistently infected human oligodendroglial (OL/BDV) cells and that the BDV P protein, but not the X protein, directly inhibited miR-155 expression in cells. When miR-155 was over-expressed, the inhibition of type I IFNs by BDV in cells was reversed, and the expression of type I IFNs was increased. When miR-155 expression was specifically blocked, cellular IFN expression and the induction of IFN by poly I:C treatment were suppressed. Furthermore, miR-155 promoted type I IFN production by targeting suppressor of cytokine signaling 1 (SOCS1) and SOCS3. Mutations in the nt1138-nt1158 region of SOCS3 abandoned the impact of miR-155 on the expression of SOCS3-enhanced green fluorescent protein (EGFP). The levels of BDV P mRNA and protein were significantly decreased in OL/BDV cells when miR-155 was over-expressed; however, miR-155-mutation did not affect the expression of BDV P-EGFP. Thus, BDV persistent infection inhibited the expression of type I IFNs through the suppression of miR-155, and miR-155 played an important immune regulatory role in BDV persistent infection. (c) 2013 Elsevier B.V. All rights reserved.