虫媒病毒是人类和动物的病原体。更好地了解这些病原体和节肢动物媒介之间的相互作用,比如蚊子,传播它们对于开发新的控制措施是必要的。蚊子载体中的主要抗病毒途径是外源小干扰RNA(exo-siRNA)途径,这是由感染细胞中的虫媒病毒衍生的双链RNA诱导的。尽管最近的工作已经显示了Argonaute-2(Ago-2)和Dicer-2(Dcr-2)在该途径中的关键作用,控制这些途径的调节机制尚未在蚊子中进行研究。这里,我们表明,Domino直系同源蛋白p400对埃及伊蚊来源的细胞中的甲病毒Semliki森林病毒(Togaviridae)具有抗病毒活性,并在体内对基孔肯雅病毒(Togaviridae)和Bunyamwera病毒(Peribunyaviridae)具有抗病毒活性。发现p400在蚊子组织中表达,并在埃及伊蚊中调节ago-2而不是dcr-2转录水平。这些发现为重要的aedineexo-siRNA途径效应蛋白的调控提供了新的见解,Ago-2,由Domino直系同源p400。他们为以前对果蝇中这种蛋白质的抗病毒和RNA干扰调节活性的观察增加了功能见解重要性雌性埃及伊蚊是人类感染节肢动物传播病毒(虫媒病毒)的载体。近几十年来,节肢动物传播的病毒感染的发病率急剧增加。矢量能力受许多因素的影响,包括蚊子的抗病毒防御。外源小干扰RNA(siRNA)通路是限制虫媒病毒在蚊子中的主要抗病毒应答。虽然这一途径的效应子的作用,Argonaute-2和Dicer-2具有良好的特性,对蚊子的调节一无所知。在这项研究中,我们证明了A.aegyptip400,其在果蝇中的直系同源Domino是Tip60复合物的染色质重塑ATPase成员,调节siRNA途径活性并控制ago-2表达水平。此外,我们发现p400对不同的虫媒病毒有抗病毒活性。因此,我们的研究为埃及伊蚊抗病毒反应的调节提供了新的见解。
Arboviruses are pathogens of humans and animals. A better understanding of the interactions between these pathogens and the arthropod vectors, such as mosquitoes, that transmit them is necessary to develop novel control measures. A major antiviral pathway in the mosquito vector is the exogenous small interfering RNA (exo-siRNA) pathway, which is induced by arbovirus-derived double-stranded RNA in infected cells. Although recent work has shown the key role played by Argonaute-2 (Ago-2) and Dicer-2 (Dcr-2) in this pathway, the regulatory mechanisms that govern these pathways have not been studied in mosquitoes. Here, we show that the Domino ortholog
p400 has antiviral activity against the alphavirus Semliki Forest virus (Togaviridae) both in Aedes aegypti-derived cells and in vivo Antiviral activity of
p400 was also demonstrated against chikungunya virus (Togaviridae) and Bunyamwera virus (Peribunyaviridae) but not Zika virus (Flaviviridae). p400 was found to be expressed across mosquito tissues and regulated ago-2 but not dcr-2 transcript levels in A. aegypti mosquitoes. These findings provide novel insights into the regulation of an important aedine exo-siRNA pathway effector protein, Ago-2, by the Domino ortholog
p400. They add functional insights to previous observations of this protein\'s antiviral and RNA interference regulatory activities in Drosophila melanogasterIMPORTANCE Female Aedes aegypti mosquitoes are vectors of human-infecting arthropod-borne viruses (arboviruses). In recent decades, the incidence of arthropod-borne viral infections has grown dramatically. Vector competence is influenced by many factors, including the mosquito\'s antiviral defenses. The exogenous small interfering RNA (siRNA) pathway is a major antiviral response restricting arboviruses in mosquitoes. While the roles of the effectors of this pathway, Argonaute-2 and Dicer-2 are well characterized, nothing is known about its regulation in mosquitoes. In this study, we demonstrate that A. aegypti
p400, whose ortholog Domino in Drosophila melanogaster is a chromatin-remodeling ATPase member of the Tip60 complex, regulates siRNA pathway activity and controls ago-2 expression levels. In addition, we found
p400 to have antiviral activity against different arboviruses. Therefore, our study provides new insights into the regulation of the antiviral response in A. aegypti mosquitoes.