RNA Interference Restricts Rift Valley Fever Virus in Multiple Insect Systems.
RNA Interference Restricts Rift Valley Fever Virus in Multiple Insect Systems.
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DOI：
10.1128/msphere.00090-17
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发表时间：
2017-05
期刊：
影响因子：
4.8
通讯作者：
Becker SC
中科院分区：
文献类型：
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作者：
Dietrich I;Jansen S;Fall G;Lorenzen S;Rudolf M;Huber K;Heitmann A;Schicht S;Ndiaye EH;Watson M;Castelli I;Brennan B;Elliott RM;Diallo M;Sall AA;Failloux AB;Schnettler E;Kohl A;Becker SC
裂谷热病毒(RVFV；PhleboVirus，Bunyaviridae)是一种新出现的人畜共患蚊媒病原体，与人和动物的健康密切相关。通过蚊媒干预RVFV传播以及预防人类和兽医疾病的成功战略，取决于更好地了解控制RVFV-媒介相互作用的机制。尽管RVFV在医学上很重要，但人们对控制RVFV在无脊椎动物宿主中复制、传播和传播的因素知之甚少。在这里，我们研究了抗病毒RNA干扰免疫途径在天然媒介蚊子和蚊细胞中防御RVFV的作用，并与模式昆虫黑腹果蝇进行了比较。我们发现，RVFV感染诱导了外源小干扰RNA(SiRNA)和piRNA途径，这有助于控制昆虫中的病毒复制。此外，我们还展示了致倦库蚊体内病毒衍生的piRNAs的产生。了解这些途径和其中的靶点，为发展以媒介为基础的新的RVFV控制措施提供了潜力。新出现的布尼亚病毒裂谷热病毒(RVFV)通过大量蚊子物种传播给人和牲畜。RNA干扰(RNAi)是蚊子用来限制正链RNA黄病毒和TOGA病毒复制的一种重要的天然免疫防御机制，但对其对抗RVFV等负链RNA病毒的作用却知之甚少。我们发现，病毒特异性小RNA在受感染的蚊子细胞、果蝇黑腹果蝇细胞中产生，最重要的是，也在RVFV媒介蚊子中产生。通过解决在成年伊蚊体内产生小RNA的问题。和致倦库蚊，我们发现不仅在伊蚊中存在病毒衍生的Piwi相互作用RNA(PiRNAs)。而且在致倦库蚊中也是如此，表明在致倦库蚊中的抗病毒RNA干扰与在伊蚊中所描述的RNAi活性相似。蚊子。我们还表明，这些化合物具有抗病毒活性，因为沉默RNAi途径效应器可以增强病毒复制。此外，我们的数据表明RVFV不编码RNAi的抑制子。这些发现表明RNAi在控制蚊子中的RVFV方面发挥了重要作用。重要裂谷热病毒(RVFV；PhleboVirus，Bunyaviridae)是一种新出现的人畜共患蚊媒病原体，与人和动物的健康密切相关。通过蚊媒干预RVFV传播以及预防人类和兽医疾病的成功战略，取决于更好地了解控制RVFV-媒介相互作用的机制。尽管RVFV在医学上很重要，但人们对控制RVFV在无脊椎动物宿主中复制、传播和传播的因素知之甚少。在这里，我们研究了抗病毒RNA干扰免疫途径在天然媒介蚊子和蚊细胞中防御RVFV的作用，并与模式昆虫黑腹果蝇进行了比较。我们发现，RVFV感染诱导了外源小干扰RNA(SiRNA)和piRNA途径，这有助于控制昆虫中的病毒复制。此外，我们还展示了致倦库蚊体内病毒衍生的piRNAs的产生。了解这些途径和其中的靶点，为发展以媒介为基础的新的RVFV控制措施提供了潜力。
Rift Valley fever virus (RVFV; Phlebovirus, Bunyaviridae) is an emerging zoonotic mosquito-borne pathogen of high relevance for human and animal health. Successful strategies of intervention in RVFV transmission by its mosquito vectors and the prevention of human and veterinary disease rely on a better understanding of the mechanisms that govern RVFV-vector interactions. Despite its medical importance, little is known about the factors that govern RVFV replication, dissemination, and transmission in the invertebrate host. Here we studied the role of the antiviral RNA interference immune pathways in the defense against RVFV in natural vector mosquitoes and mosquito cells and draw comparisons to the model insect Drosophila melanogaster. We found that RVFV infection induces both the exogenous small interfering RNA (siRNA) and piRNA pathways, which contribute to the control of viral replication in insects. Furthermore, we demonstrate the production of virus-derived piRNAs in Culex quinquefasciatus mosquitoes. Understanding these pathways and the targets within them offers the potential of the development of novel RVFV control measures in vector-based strategies. The emerging bunyavirus Rift Valley fever virus (RVFV) is transmitted to humans and livestock by a large number of mosquito species. RNA interference (RNAi) has been characterized as an important innate immune defense mechanism used by mosquitoes to limit replication of positive-sense RNA flaviviruses and togaviruses; however, little is known about its role against negative-strand RNA viruses such as RVFV. We show that virus-specific small RNAs are produced in infected mosquito cells, in Drosophila melanogaster cells, and, most importantly, also in RVFV vector mosquitoes. By addressing the production of small RNAs in adult Aedes sp. and Culex quinquefasciatus mosquitoes, we showed the presence of virus-derived Piwi-interacting RNAs (piRNAs) not only in Aedes sp. but also in C. quinquefasciatus mosquitoes, indicating that antiviral RNA interference in C. quinquefasciatus mosquitoes is similar to the described activities of RNAi in Aedes sp. mosquitoes. We also show that these have antiviral activity, since silencing of RNAi pathway effectors enhances viral replication. Moreover, our data suggest that RVFV does not encode a suppressor of RNAi. These findings point toward a significant role of RNAi in the control of RVFV in mosquitoes. IMPORTANCE Rift Valley fever virus (RVFV; Phlebovirus, Bunyaviridae) is an emerging zoonotic mosquito-borne pathogen of high relevance for human and animal health. Successful strategies of intervention in RVFV transmission by its mosquito vectors and the prevention of human and veterinary disease rely on a better understanding of the mechanisms that govern RVFV-vector interactions. Despite its medical importance, little is known about the factors that govern RVFV replication, dissemination, and transmission in the invertebrate host. Here we studied the role of the antiviral RNA interference immune pathways in the defense against RVFV in natural vector mosquitoes and mosquito cells and draw comparisons to the model insect Drosophila melanogaster. We found that RVFV infection induces both the exogenous small interfering RNA (siRNA) and piRNA pathways, which contribute to the control of viral replication in insects. Furthermore, we demonstrate the production of virus-derived piRNAs in Culex quinquefasciatus mosquitoes. Understanding these pathways and the targets within them offers the potential of the development of novel RVFV control measures in vector-based strategies.