Host-virus molecular arms race: RNAi-mediated antiviral defense and viral suppressor of RNAi

Cell insight Pub Date : 2025-08-27 DOI:10.1016/j.cellin.2025.100276

Bowen Zhang , Xi Zhou , Yujie Ren

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Abstract

RNA interference (RNAi) is a highly conserved post-transcriptional gene silencing (PTGS) mechanism widely presented in eukaryotes. During viral infection, double-stranded RNA viral replicative intermediate (vRI-dsRNA) derived from the viral genome is recognized and processed by Dicer to generate small interfering RNA (siRNA). The viral siRNA (vsiRNA) is subsequently loaded into the RNA-induced silencing complex (RISC), which targets and degrades viral RNAs to achieve antiviral immune response. During long-term evolution, viruses have evolved to counteract RNAi by encoding viral suppressors of RNAi (VSRs) through various strategies, thereby evading the immune clearance. Here we review how VSRs function as immune evasion factors against antiviral RNAi, along with their evolutionary significance in shaping both viral adaptation and host-pathogen co-evolution. We also discuss recent advancements and unresolved controversies regarding RNAi-mediated antiviral immunity in mammals. Finally, we provide a comprehensive analysis of emerging therapeutic strategies and vaccine designs that leverage the RNAi-VSR interaction mechanisms, while addressing their potential prospects and challenges in clinical translation.

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宿主-病毒分子军备竞赛：RNAi介导的抗病毒防御和RNAi的病毒抑制因子

RNA干扰（RNAi）是一种高度保守的转录后基因沉默（PTGS）机制，广泛存在于真核生物中。在病毒感染过程中，来自病毒基因组的双链RNA病毒复制中间体（vRI-dsRNA）被Dicer识别并加工生成小干扰RNA （siRNA）。病毒siRNA （vsiRNA）随后被装载到rna诱导沉默复合体（RISC）中，该复合体靶向并降解病毒rna以实现抗病毒免疫反应。在长期的进化过程中，病毒通过各种策略通过编码RNAi的病毒抑制因子（VSRs）来对抗RNAi，从而逃避免疫清除。在这里，我们回顾了VSRs作为抗病毒RNAi的免疫逃避因子的功能，以及它们在塑造病毒适应和宿主-病原体共同进化中的进化意义。我们还讨论了哺乳动物rnai介导的抗病毒免疫的最新进展和未解决的争议。最后，我们全面分析了利用RNAi-VSR相互作用机制的新兴治疗策略和疫苗设计，同时阐述了它们在临床转化中的潜在前景和挑战。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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