Expression of the zinc-finger antiviral protein inhibits alphavirus replication
Expression of the zinc-finger antiviral protein inhibits alphavirus replication
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DOI：
10.1128/jvi.77.21.11555-11562.2003
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发表时间：
2003-11-01
影响因子：
5.4
通讯作者：
MacDonald, MR
中科院分区：
文献类型：
--
作者：
Bick, MJ;Carroll, JWN;MacDonald, MR
大鼠锌指抗病毒蛋白(ZAP)是近年来发现的一种能抵抗逆转录病毒感染的宿主蛋白。我们分析了ZAP抑制其他家族病毒的能力，发现ZAP有效地抑制了Togaviridae内甲型病毒属多个成员的复制，包括Sindbis病毒、Semliki森林病毒、罗斯河病毒和委内瑞拉马脑炎病毒。然而，ZAP的表达并没有诱导出广谱的抗病毒状态，因为一些病毒，包括水泡性口炎病毒、脊髓灰质炎病毒、黄热病病毒和1型单纯疱疹病毒在表达ZAP的细胞中复制到正常水平。我们确定ZAP的表达在病毒侵入和进入后，但在新合成的正链基因组RNA扩增之前，抑制了Sindbis病毒的复制。利用一个表达荧光素酶的温度敏感的Sindbis病毒突变体，我们进一步证明了ZAP的表达阻止了传入病毒RNA的翻译。阐明ZAP抑制Sindbis病毒翻译的抗病毒机制可能会导致开发出具有广泛抗甲病毒活性的药物。
The rat zinc-finger antiviral protein (ZAP) was recently identified as a host protein conferring resistance to retroviral infection. We analyzed ZAP's ability to inhibit viruses from other families and found that ZAP potently inhibits the replication of multiple members of the Alphavirus genus within the Togaviridae, including Sindbis virus, Semliki Forest virus, Ross River virus, and Venezuelan equine encephalitis virus. However, expression of ZAP did not induce a broad-spectrum antiviral state as some viruses, including vesicular stomatitis virus, poliovirus, yellow fever virus, and herpes simplex virus type 1, replicated to normal levels in ZAP-expressing cells. We determined that ZAP expression inhibits Sindbis virus replication after virus penetration and entry, but before the amplification of newly synthesized plus strand genomic RNA. Using a temperature-sensitive Sindbis virus mutant expressing luciferase, we further showed that translation of incoming viral RNA is blocked by ZAP expression. Elucidation of the antiviral mechanism by which ZAP inhibits Sindbis virus translation may lead to the development of agents with broad activity against alphaviruses.