The Antiviral RNAi Response in Vector and Non-vector Cells against Orthobunyaviruses.
The Antiviral RNAi Response in Vector and Non-vector Cells against Orthobunyaviruses.
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载体和非载体细胞对正胞厅病毒的抗病毒RNAi反应。
DOI：
10.1371/journal.pntd.0005272
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发表时间：
2017-01
影响因子：
3.8
通讯作者：
Schnettler E
中科院分区：
文献类型：
--
作者：
Dietrich I;Shi X;McFarlane M;Watson M;Blomström AL;Skelton JK;Kohl A;Elliott RM;Schnettler E
媒介节肢动物通过包括RNA干扰（RNAi）途径在内的抗病毒先天免疫应答来控制虫媒病毒的复制和传播。虫媒病毒感染已显示诱导外源性小干扰RNA（siRNA）和Piwi相互作用RNA（皮尔纳）途径，但这些宿主应答在蚊子细胞中的直接抗病毒活性仅针对有限数量的正链RNA虫媒病毒被证明。对于布尼亚病毒，小RNA途径在抗病毒防御中的相对贡献是未知的。布尼亚病毒科中的正布尼亚病毒属携带多种蚊媒、蠓媒和蜱媒虫媒病毒。我们假设载体细胞与非载体细胞中的抗病毒RNAi反应可能存在差异，这可能影响病毒宿主范围。使用埃及伊蚊衍生的蚊子细胞，蚊子传播的正布尼亚病毒和蚊传播的正布尼亚病毒，我们表明，布尼亚病毒感染通常诱导小RNA的产生和小RNA途径对单个病毒的影响在特定的载体-虫媒病毒相互作用中不同。这些发现对于我们理解抗病毒RNAi途径和正布尼亚病毒-载体相互作用和向性具有重要意义。奥罗普什病毒、拉克罗斯病毒和施马伦贝格病毒等正布尼亚病毒是由节肢动物传播的重要全球性人畜病原体。进一步了解节肢动物媒介中的抗病毒控制机制是开发基于预防传播的新型预防策略的关键。抗病毒小RNA途径如外源性siRNA和皮尔纳途径已显示介导针对正链RNA虫媒病毒的抗病毒活性，但关于其针对负链RNA虫媒病毒的活性的信息严重缺乏。在这里，我们表明，在埃及伊蚊衍生的蚊子细胞，蚊子传播的正布尼亚病毒的抗病毒反应主要是由siRNA和皮尔纳途径介导的，而皮尔纳途径在控制蚊传播的正布尼亚病毒中只起很小的作用。这表明载体特异性部分地由依赖于宿主物种的抗病毒反应控制。这些发现有助于我们理解虫媒病毒-载体相互作用。
Vector arthropods control arbovirus replication and spread through antiviral innate immune responses including RNA interference (RNAi) pathways. Arbovirus infections have been shown to induce the exogenous small interfering RNA (siRNA) and Piwi-interacting RNA (piRNA) pathways, but direct antiviral activity by these host responses in mosquito cells has only been demonstrated against a limited number of positive-strand RNA arboviruses. For bunyaviruses in general, the relative contribution of small RNA pathways in antiviral defences is unknown. The genus Orthobunyavirus in the Bunyaviridae family harbours a diverse range of mosquito-, midge- and tick-borne arboviruses. We hypothesized that differences in the antiviral RNAi response in vector versus non-vector cells may exist and that could influence viral host range. Using Aedes aegypti-derived mosquito cells, mosquito-borne orthobunyaviruses and midge-borne orthobunyaviruses we showed that bunyavirus infection commonly induced the production of small RNAs and the effects of the small RNA pathways on individual viruses differ in specific vector-arbovirus interactions. These findings have important implications for our understanding of antiviral RNAi pathways and orthobunyavirus-vector interactions and tropism. A number of orthobunyaviruses such as Oropouche virus, La Crosse virus and Schmallenberg virus are important global human or animal pathogens transmitted by arthropod vectors. Further understanding of the antiviral control mechanisms in arthropod vectors is key to developing novel prevention strategies based on preventing transmission. Antiviral small RNA pathways such as the exogenous siRNA and piRNA pathways have been shown to mediate antiviral activity against positive-strand RNA arboviruses, but information about their activities against negative-strand RNA arboviruses is critically lacking. Here we show that in Aedes aegypti-derived mosquito cells, the antiviral responses to mosquito-borne orthobunyaviruses is largely mediated by both siRNA and piRNA pathways, whereas the piRNA pathway plays only a minor role in controlling midge-borne orthobunyaviruses. This suggests that vector specificity is in part controlled by antiviral responses that depend on the host species. These findings contribute significantly to our understanding of arbovirus-vector interactions.