Eukaryotic initiation factor 4AI interacts with NS4A of Dengue virus and plays an antiviral role
Eukaryotic initiation factor 4AI interacts with NS4A of Dengue virus and plays an antiviral role
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真核起始因子4AI与登革热病毒的NS4A相互作用，发挥抗病毒作用。
DOI：
10.1016/j.bbrc.2015.04.004
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发表时间：
2015-05-22
影响因子：
3.1
通讯作者：
Zhang, Ping
中科院分区：
文献类型：
--
作者：
Chen, Xiaoyan;Xia, Jun;Zhang, Ping
登革热病毒（DENV）是一种蚊媒黄病毒，在热带和亚热带地区引起最流行的疾病。DENV利用宿主因子促进其复制，而宿主细胞意图抑制病毒复制。DENV的NS4A在病毒复制过程中起着至关重要的作用。为了鉴定更多被NS4A募集的细胞蛋白，我们进行了串联亲和纯化实验。质谱数据显示，人真核起始因子4AI （eIF4AI）是ns4a潜在的相互作用伙伴之一。共免疫沉淀数据证实了NS4A和elF4AI之间的相互作用，并且elF4A1的n端atp结合域和c端解旋酶域都参与了它们的相互作用。功能上，RNAi沉默eIF4AI可显著提高DENV1、DENV2和DENV3的复制水平。elF4A1的敲低显著减弱了DENV2感染诱导的dsRNA-activated （PKR）和elF2a蛋白激酶的磷酸化。总的来说，这些数据表明NS4A在拮抗宿主抗病毒防御中的潜在作用是通过招募elF4AI并逃避PKR介导的翻译抑制。(C) 2015爱思唯尔公司版权所有。
Dengue virus (DENV) is a mosquito-borne flavivirus that causes the most prevalent diseases in tropical and subtropical regions. DENV utilizes host factors to facilitate its replication, while host cells intend to restrain virus replication. NS4A of DENV has been implicated to play a crucial role during viral replication. To identify more cellular proteins that are recruited by NS4A, we carried out a tandem affinity purification assay. The mass spectrometry data revealed that human eukaryotic initiation factor 4AI (eIF4AI) was one of potential NS4A-interacting partners. Co-immunoprecipitation data confirmed the interaction between NS4A and elF4AI, and both the N-terminal ATP-binding domain and C-terminal helicase domain of elF4A1 were involved in their association. Functionally, silencing of eIF4AI by RNAi significantly increased the replication level of DENV1, DENV2 and DENV3. And knockdown of elF4A1 markedly attenuated the phosphorylation of protein kinase regulated by dsRNA-activated (PKR) and elF2a induced by DENV2 infection. Collectively, these data suggested that a potential role of NS4A in antagonizing host antiviral defense is by recruiting elF4AI and escaping the translation inhibition mediated by PKR. (C) 2015 Elsevier Inc. All rights reserved.