Department of Entomology, Fralin Life Science Institute, Virginia Tech, Blacksburg, Virginia, United States of America.
PLoS Pathog. 2012 Jan;8(1):e1002470. doi: 10.1371/journal.ppat.1002470. Epub 2012 Jan 5.
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.
许多蚊媒病原体的自然维持周期需要在无脊椎宿主中建立持续的非致死性感染。这一过程的机制尚不清楚，但我们之前曾表明，由小干扰 RNA（siRNA）介导的抗病毒反应在调节蚊媒中黄病毒感染的发病机制方面很重要。然而，我们在这里报告说，感染蚊子的黄病毒也会触发另一类病毒衍生的小 RNA 的产生，这些小 RNA 表现出与依赖乒乓效应的 piwi 相互作用 RNA（piRNA）许多相似之处。然而，与之前从重复元件或 piRNA 簇中描述的依赖乒乓效应的 piRNA 不同，我们的工作表明这些小 RNA 是在体产生的。我们还提供了证据表明，病毒衍生的 piRNA 样小 RNA 能够调节在缺乏病毒 siRNA 产生的 dicer-2 缺失突变体蚊细胞系中黄病毒感染的发病机制。总的来说，我们的结果表明，非典型的 piRNA 途径存在于载体蚊子的体中，并且可能与 siRNA 途径冗余，以靶向黄病毒复制。
