Production of virus-derived ping-pong-dependent piRNA-like small RNAs in the mosquito soma.
Production of virus-derived ping-pong-dependent piRNA-like small RNAs in the mosquito soma.
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DOI：
10.1371/journal.ppat.1002470
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发表时间：
2012-01
期刊：
影响因子：
6.7
通讯作者：
Myles KM
中科院分区：
文献类型：
--
作者：
Morazzani EM;Wiley MR;Murreddu MG;Adelman ZN;Myles KM
许多蚊媒病原体的自然维持周期要求在无脊椎动物宿主中建立持续的非致命性感染。发生这种情况的机制尚不清楚，但我们先前已经证明，由小干扰RNA(SiRNAs)指导的抗病毒反应在调节蚊子甲型病毒感染的发病机制中是重要的。然而，我们在这里报告，感染甲型病毒的蚊子也会触发另一类病毒衍生的小RNA的产生，这种小RNA与乒乓球依赖的piwi相互作用RNA(PiRNAs)有许多相似之处。然而，与先前描述的来自重复元件或piRNA簇的乒乓球依赖的piRNA不同，我们的工作表明在胞体中产生。我们还提出了证据表明，病毒衍生的piRNA样小RNA能够调节DICER-2缺失突变蚊子细胞系中甲型病毒感染的发病机制，这些突变的蚊子细胞系在病毒siRNA产生方面存在缺陷。总体而言，我们的结果表明，媒介蚊体中存在非规范的piRNA途径，并且可能与siRNA途径冗余地作用于靶向甲型病毒复制的siRNA途径。蚊子通过先天免疫反应保护自己免受病毒感染。因此，蚊媒病毒疾病，如西尼罗热、登革热和基孔肯雅热，只有在病原体克服这些防御时才会传播给人类。尽管如此，人们对蚊子的免疫途径知之甚少。我们以前已经证明，在蚊子载体中存在由小干扰RNA(SiRNAs)引导的抗病毒反应。然而，我们在这里表明，另一类病毒衍生的小RNA，显示出许多类似于乒乓球依赖的piwi相互作用RNA(PiRNAs)，也在蚊子的胞体中产生。我们还表明，这些类似piRNA的小RNA能够在基于siRNA免疫缺陷的蚊子细胞系中建立抗病毒防御，这表明蚊子具有多余的基于RNA的抗病毒反应。这项研究为蚊子的免疫防御如何限制病毒复制和蚊媒病毒的传播提供了新的见解。
The natural maintenance cycles of many mosquito-borne pathogens require establishment of persistent non-lethal infections in the invertebrate host. The mechanism by which this occurs is not well understood, but we have previously shown that an antiviral response directed by small interfering RNAs (siRNAs) is important in modulating the pathogenesis of alphavirus infections in the mosquito. However, we report here that infection of mosquitoes with an alphavirus also triggers the production of another class of virus-derived small RNAs that exhibit many similarities to ping-pong-dependent piwi-interacting RNAs (piRNAs). However, unlike ping-pong-dependent piRNAs that have been described previously from repetitive elements or piRNA clusters, our work suggests production in the soma. We also present evidence that suggests virus-derived piRNA-like small RNAs are capable of modulating the pathogenesis of alphavirus infections in dicer-2 null mutant mosquito cell lines defective in viral siRNA production. Overall, our results suggest that a non-canonical piRNA pathway is present in the soma of vector mosquitoes and may be acting redundantly to the siRNA pathway to target alphavirus replication. Mosquitoes defend themselves against viral infection with an innate immune response. Thus, mosquito-borne viral diseases like West Nile fever, dengue fever, and chikungunya fever are transmitted to humans only when the pathogen overcomes these defenses. Despite this, relatively little is known about the immune pathways of the mosquito. We have previously shown that an antiviral response directed by small interfering RNAs (siRNAs) is present in culicine mosquito vectors. However, we show here that another class of virus-derived small RNAs, exhibiting many similarities with ping-pong-dependent piwi-interacting RNAs (piRNAs), is also produced in the soma of culicine mosquitoes. We also show that these piRNA-like small RNAs are capable of mounting an antiviral defense in mosquito cell lines with defective siRNA-based immunity, suggesting that mosquitoes possess redundant RNA-based antiviral responses. This study provides new insights into how a mosquito's immune defenses restrict virus replication and the transmission of mosquito-borne viruses.
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