Characterization of the Zika virus induced small RNA response in Aedes aegypti cells.
Characterization of the Zika virus induced small RNA response in Aedes aegypti cells.
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DOI：
10.1371/journal.pntd.0006010
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发表时间：
2017-10
影响因子：
3.8
通讯作者：
Kohl A
中科院分区：
文献类型：
--
作者：
Varjak M;Donald CL;Mottram TJ;Sreenu VB;Merits A;Maringer K;Schnettler E;Kohl A
RNA干扰（RNAi）控制蚊子中的虫媒病毒感染。两种不同的RNAi途径参与抗病毒反应：PIWI相互作用RNA（皮尔纳）和外源性短干扰RNA（exo-siRNA）途径，其特征在于分别产生25-29和21个核苷酸的病毒衍生的小RNA。exo-siRNA途径被认为是蚊子抗病毒反应的关键机制。在埃及伊蚊衍生的细胞中，产生了寨卡病毒（ZIKV）特异性siRNA并将其加载到exo-siRNA途径效应蛋白Argonaute 2（Ago 2）中;尽管Ago 2的敲低并未增强病毒复制。在Dcr 2敲除细胞系中观察到增强的ZIKV复制，表明exo-siRNA途径涉及抗病毒应答。尽管检测到ZIKV特异性piRNA大小的小RNA，但这些小RNA缺乏特征性皮尔纳乒乓签名基序，并且结合至Ago 3而不是Piwi 5或Piwi 6。PIWI蛋白的沉默表明Ago 3、Piwi 5或Piwi 6的敲低不增强ZIKV复制，并且仅Piwi 4显示抗病毒活性。我们还报道了ZIKV衣壳（C）蛋白的表达放大了报告甲病毒的复制;尽管与黄热病病毒C蛋白不同，它不抑制exo-siRNA途径。我们的研究结果阐明了ZIKV-蚊子RNAi相互作用，这对于理解其传播至关重要。寨卡病毒（ZIKV）是寨卡病毒的一种常见类型。ZIKV由埃及伊蚊传播，因此了解病毒-载体相互作用很重要。蚊子细胞中ZIKV感染的分析表明，在感染期间涉及两种RNA干扰途径：外源性短干扰（si）RNA（exo-siRNA）和PIWI相互作用（pi）RNA途径。如果Dcr 2（一种负责将dsRNA切割成siRNA的酶）被敲除，则与对照细胞相比，ZIKV复制增加。然而，Ago 2表达的敲低对ZIKV复制没有显著的增强作用。在PIWI途径的情况下，仅发现Piwi 4蛋白具有显著的抗病毒活性。此外，与黄热病病毒的衣壳（C）蛋白不同，ZIKV衣壳蛋白不抑制siRNA途径。这些结果表明，ZIKV具有逃避蚊子先天免疫的机制，因此了解这些病毒-载体相互作用及其对传播的影响非常重要。
RNA interference (RNAi) controls arbovirus infections in mosquitoes. Two different RNAi pathways are involved in antiviral responses: the PIWI-interacting RNA (piRNA) and exogenous short interfering RNA (exo-siRNA) pathways, which are characterized by the production of virus-derived small RNAs of 25–29 and 21 nucleotides, respectively. The exo-siRNA pathway is considered to be the key mosquito antiviral response mechanism. In Aedes aegypti-derived cells, Zika virus (ZIKV)-specific siRNAs were produced and loaded into the exo-siRNA pathway effector protein Argonaute 2 (Ago2); although the knockdown of Ago2 did not enhance virus replication. Enhanced ZIKV replication was observed in a Dcr2-knockout cell line suggesting that the exo-siRNA pathway is implicated in the antiviral response. Although ZIKV-specific piRNA-sized small RNAs were detected, these lacked the characteristic piRNA ping-pong signature motif and were bound to Ago3 but not Piwi5 or Piwi6. Silencing of PIWI proteins indicated that the knockdown of Ago3, Piwi5 or Piwi6 did not enhance ZIKV replication and only Piwi4 displayed antiviral activity. We also report that the expression of ZIKV capsid (C) protein amplified the replication of a reporter alphavirus; although, unlike yellow fever virus C protein, it does not inhibit the exo-siRNA pathway. Our findings elucidate ZIKV-mosquito RNAi interactions that are important for understanding its spread. The recent outbreak of Zika virus (ZIKV) in the Americas has resulted in a severe threat to public health. ZIKV is transmitted by Aedes aegypti mosquitoes, thus it is important to understand virus-vector interactions. Analysis of ZIKV infection in mosquito cells indicated that two RNA interference pathways are involved during infection: the exogenous short-interfering (si)RNA (exo-siRNA) and PIWI-interacting (pi)RNA pathways. If Dcr2, an enzyme responsible for cleaving dsRNA into siRNAs, is knocked out, ZIKV replication is increased compared to control cells. However, the knockdown of Ago2 expression had no significant enhancing effect on ZIKV replication. In the case of the PIWI pathway, only the Piwi4 protein was found to have significant antiviral activity. Furthermore, unlike the capsid (C) protein of yellow fever virus, ZIKV capsid protein does not suppress the siRNA pathway. These results suggest that ZIKV has mechanisms to evade mosquito innate immunity and it is therefore important to understand these virus-vector interactions and the implications they have on transmission.
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影响因子：
3.4
作者：
Cumberworth SL;Clark JJ;Kohl A;Donald CL
通讯作者：
Donald CL
影响因子：
4.2
作者：
Campbell CL;Keene KM;Brackney DE;Olson KE;Blair CD;Wilusz J;Foy BD
通讯作者：
Foy BD
DOI：
10.3390/v7020820
发表时间：
2015-02-17
期刊：
Viruses
影响因子：
--
作者：
Blair CD;Olson KE
通讯作者：
Olson KE
影响因子：
5.4
作者：
Leger, P.;Lara, E.;Bouloy, M.
通讯作者：
Bouloy, M.
DOI：
10.1073/pnas.0813412106
发表时间：
2009-03-31
影响因子：
11.1
作者：
Flynt, Alex;Liu, Na;Lai, Eric C.
通讯作者：
Lai, Eric C.