Role of zinc-finger anti-viral protein in host defense against Sindbis virus.
Role of zinc-finger anti-viral protein in host defense against Sindbis virus.
复制标题
DOI：
10.1093/intimm/dxv010
复制
发表时间：
2015-07
影响因子：
4.4
通讯作者：
Tatsuya Kozaki;Michihiro Takahama;Takuma Misawa;Y. Matsuura;S. Akira;T. Saitoh
中科院分区：
文献类型：
--
作者：
Tatsuya Kozaki;Michihiro Takahama;Takuma Misawa;Y. Matsuura;S. Akira;T. Saitoh
越来越多的证据表明，I型干扰素（IFN）介导宿主对RNA病毒的保护性反应。然而，参与这种反应的抗病毒效应分子尚未完全确定。在这里，我们表明，锌指抗病毒蛋白（ZAP），干扰素诱导基因，在体外和体内消除辛德毕斯病毒（SINV）中起着关键作用。ZAP的丢失大大增强了SINV的复制，但不抑制I型IFN在原代小鼠胚胎成纤维细胞（MEF）中的产生。ZAP结合SINV RNA并使其不稳定，从而抑制SINV的复制。I型IFN不能抑制ZAP缺陷型MEFs中的SINV复制，而ZAP的异位表达足以抑制缺乏I型IFN和IFN诱导基因表达的MEFs中的SINV复制。ZAP缺陷型小鼠对SINV感染高度敏感，尽管它们产生足够量的I型IFN。因此，ZAP是介导I型IFN依赖性宿主防御SINV的RNA敏感抗病毒效应分子。
Accumulating evidence indicates that type I interferon (IFN) mediates the host protective response to RNA viruses. However, the anti-viral effector molecules involved in this response have not been fully identified. Here, we show that zinc-finger anti-viral protein (ZAP), an IFN-inducible gene, plays a critical role in the elimination of Sindbis virus (SINV) in vitro and in vivo. The loss of ZAP greatly enhances the replication of SINV but does not inhibit type I IFN production in primary mouse embryonic fibroblasts (MEFs). ZAP binds and destabilizes SINV RNA, thereby suppressing the replication of SINV. Type I IFN fails to suppress SINV replication in ZAP-deficient MEFs, whereas the ectopic expression of ZAP is sufficient to suppress the replication of SINV in MEFs lacking the expression of type I IFN and the IFN-inducible genes. ZAP-deficient mice are highly susceptible to SINV infection, although they produce sufficient amounts of type I IFN. Therefore, ZAP is an RNA-sensing anti-viral effector molecule that mediates the type-I-IFN-dependent host defense against SINV.