MCPIP1 inhibits coxsackievirus B3 replication by targeting viral RNA and negatively regulates virus-induced inflammation
MCPIP1 inhibits coxsackievirus B3 replication by targeting viral RNA and negatively regulates virus-induced inflammation
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MCPIP1 通过靶向病毒 RNA 抑制柯萨奇病毒 B3 复制并负向调节病毒诱导的炎症
DOI：
10.1007/s00430-017-0523-0
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发表时间：
2018
影响因子：
5.4
通讯作者：
Xu Wei
中科院分区：
文献类型：
--
作者：
Li Min;Yan Kepeng;Wei Lin;Yang Yang;Qian Qian;Xu Wei
单核细胞趋化蛋白诱导蛋白1（MCPIP 1）是一种重要的免疫炎症调节因子。MCPIP 1对日本脑炎等多种病毒具有抗病毒活性。然而，其在柯萨奇病毒B3（CVB3）感染（一种正链RNA病毒）中的作用尚未得到解决。在这里，我们报道了MCPIP 1在心肌细胞中被CVB 3感染以及在感染小鼠的心脏和胰腺中上调。我们发现MCPIP1的过表达抑制了CVB3的复制，而敲低MCPIP1则促进了CVB3的复制。荧光素酶实验表明，MCPIP1靶向CVB3 3′UTR的非ARE区，其作用依赖于RNA酶、RNA结合和寡聚化能力，而不依赖于去泛素化酶活性。我们进一步证实了MCPIP1负调控巨噬细胞中CVB3诱导的炎症反应。因此，我们的数据表明，MCPIP 1作为一个有效的宿主防御CVB 3感染和病毒性心肌炎。
Monocyte chemotactic protein-induced protein 1(MCPIP1) is identified as an important inflammatory regulator during immune response. MCPIP1 possesses antiviral activities against several viruses, such as Japanese encephalitis. However, its role on Coxsackievirus B3 (CVB3) infection, a positive-stranded RNA virus, has not been addressed. Here, we reported that MCPIP1 was up-regulated in cardiomyocytes by CVB3 infection and in hearts and pancreas of infected mice. Then we found that overexpression of MCPIP1 inhibited CVB3 replication and knockdown of it promoted virus replication. Luciferase assay demonstrated MCPIP1 targeting non-ARE region of CVB3 3′UTR, which was dependent on its RNase, RNA binding and oligomerization abilities, but not deubiquitinase activity. We further verified that MCPIP1 negatively regulated CVB3-induced inflammatory response in macrophages. Thus, our data suggest MCPIP1 as a potent host defense against CVB3 infection and viral myocarditis.