Zinc finger antiviral protein inhibits coxsackievirus B3 virus replication and protects against viral myocarditis
Zinc finger antiviral protein inhibits coxsackievirus B3 virus replication and protects against viral myocarditis
复制标题
锌指抗病毒蛋白抑制柯萨奇病毒 B3 病毒复制并预防病毒性心肌炎
DOI：
10.1016/j.antiviral.2015.09.001
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发表时间：
2015-11-01
影响因子：
7.6
通讯作者：
Xu, Wei
中科院分区：
文献类型：
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作者：
Li, Min;Yan, Kepeng;Xu, Wei
据报道，宿主锌指抗病毒蛋白（ZAP）对正链RNA病毒（托加病毒科）、负链RNA病毒（丝状病毒科）和逆转录病毒（逆转录病毒科）具有抗病毒活性。然而，ZAP是否限制肠病毒感染和肠病毒介导疾病的发展仍然未知。在这里，我们报道了ZAP对柯萨奇病毒B3 （CVB3）的抗病毒特性，柯萨奇病毒B3是小核糖核酸病毒科Enterovints属的单链RNA病毒，是病毒性心肌炎（VMC）的主要病原体。我们发现，CVB3感染VMC小鼠心脏组织后，ZAP的表达被显著诱导。ZAP在感染后能有效抑制细胞中CVB3的复制，而小鼠过表达ZAP通过显著减少心脏炎症细胞因子的产生，显著增加对CVB3复制和病毒性心肌炎的抵抗。zap反应元件（ZREs）被定位到病毒RNA的3'UTR和5'UTR上。综上所述，ZAP通过直接靶向病毒RNA来抵抗CVB3感染，并通过抑制病毒复制和心脏炎症细胞因子的产生来保护小鼠免受急性心肌炎的侵袭。我们的发现进一步扩大了ZAP的病毒靶点范围，提示ZAP作为CVB3引起的病毒性心肌炎的潜在治疗靶点。(C) 2015 Elsevier B.V.版权所有
The host Zinc finger antiviral protein (ZAP) has been reported exhibiting antiviral activity against positive-stranded RNA viruses (Togaviridae), negative-stranded RNA viruses (Filoviridae) and retroviruses (Retroviridae). However, whether ZAP restricts the infection of enterovirus and the development of enterovirus mediated disease remains unknown. Here, we reported the antiviral properties of ZAP against coxsackievirus B3 (CVB3), a single-stranded RNA virus of the Enterovints genus within the Picornaviridae as a major causative agent of viral myocarditis (VMC). We found that the expression of ZAP was significantly induced after CVB3 infection in heart tissues of VMC mice. ZAP potently inhibited CVB3 replication in cells after infection, while overexpression of ZAP in mice significantly increased the resistance to CVB3 replication and viral myocarditis by significantly reducing cardiac inflammatory cytokine production. The ZAP-responsive elements (ZREs) were mapped to the 3'UTR and 5'UTR of viral RNA. Taken together, ZAP confers resistance to CVB3 infection via directly targeting viral RNA and protects mice from acute myocarditis by suppressing viral replication and cardiac inflammatory cytokine production. Our finding further expands ZAP's range of viral targets, and suggests ZAP as a potential therapeutic target for viral myocarditis caused by CVB3. (C) 2015 Elsevier B.V. All rights reserved.