Swevers Luc, Kontogiannatos Dimitrios, Kolliopoulou Anna, Ren Feifei, Feng Min, Sun Jingchen
Insect Molecular Genetics and Biotechnology, Institute of Biosciences and Applications, National Centre for Scientific Research "Demokritos", Athens, Greece.
Guangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, China.
Front Physiol. 2021 Nov 11;12:749387. doi: 10.3389/fphys.2021.749387. eCollection 2021.
While RNAi is often heralded as a promising new strategy for insect pest control, a major obstacle that still remains is the efficient delivery of dsRNA molecules within the cells of the targeted insects. However, it seems overlooked that dsRNA viruses already have developed efficient strategies for transport of dsRNA molecules across tissue barriers and cellular membranes. Besides protecting their dsRNA genomes in a protective shell, dsRNA viruses also display outer capsid layers that incorporate sophisticated mechanisms to disrupt the plasma membrane layer and to translocate core particles (with linear dsRNA genome fragments) within the cytoplasm. Because of the perceived efficiency of the translocation mechanism, it is well worth analyzing in detail the molecular processes that are used to achieve this feat. In this review, the mechanism of cell entry by dsRNA viruses belonging to the family is discussed in detail. Because of the large amount of progress in mammalian versus insect models, the mechanism of infections of reoviruses in mammals (orthoreoviruses, rotaviruses, orbiviruses) will be treated as a point of reference against which infections of reoviruses in insects (orbiviruses in midges, plant viruses in hemipterans, insect-specific cypoviruses in lepidopterans) will be compared. The goal of this discussion is to uncover the basic principles by which dsRNA viruses cross tissue barriers and translocate their cargo to the cellular cytoplasm; such knowledge subsequently can be incorporated into the design of dsRNA virus-based viral-like particles for optimal delivery of RNAi triggers in targeted insect pests.
虽然RNA干扰常被誉为一种有前景的害虫防治新策略，但仍然存在的一个主要障碍是在目标昆虫细胞内有效递送双链RNA分子。然而，似乎被忽视的是，双链RNA病毒已经开发出了将双链RNA分子运输穿过组织屏障和细胞膜的有效策略。除了在保护壳中保护其双链RNA基因组外，双链RNA病毒还展示出外衣壳层，这些外衣壳层包含复杂的机制来破坏质膜层并将核心颗粒（带有线性双链RNA基因组片段）转运到细胞质中。由于转运机制的高效性，详细分析用于实现这一壮举的分子过程是非常值得的。在这篇综述中，详细讨论了属于该科的双链RNA病毒进入细胞的机制。由于在哺乳动物与昆虫模型方面取得了大量进展，呼肠孤病毒在哺乳动物（正呼肠孤病毒、轮状病毒、环状病毒）中的感染机制将作为一个参考点，与呼肠孤病毒在昆虫（蠓中的环状病毒、半翅目中的植物病毒、鳞翅目中的昆虫特异性质型多角体病毒）中的感染进行比较。本次讨论的目标是揭示双链RNA病毒跨越组织屏障并将其货物转运到细胞质中的基本原理；这些知识随后可被纳入基于双链RNA病毒的病毒样颗粒的设计中，以便在目标害虫中最佳地递送RNA干扰触发物。
