Institute of Plant Science and Resources, Okayama University, Kurashiki, Okayama 710-0046, Japan.
Proc Natl Acad Sci U S A. 2024 Jun 18;121(25):e2322765121. doi: 10.1073/pnas.2322765121. Epub 2024 Jun 12.
Antiviral RNA interference (RNAi) is conserved from yeasts to mammals. Dicer recognizes and cleaves virus-derived double-stranded RNA (dsRNA) and/or structured single-stranded RNA (ssRNA) into small-interfering RNAs, which guide effector Argonaute to homologous viral RNAs for digestion and inhibit virus replication. Thus, Argonaute is believed to be essential for antiviral RNAi. Here, we show Argonaute-independent, Dicer-dependent antiviral defense against dsRNA viruses using (chestnut blight fungus), which is a model filamentous ascomycetous fungus and hosts a variety of viruses. The fungus has two dicer-like genes ( and ) and four argonaute-like genes ( to ). We prepared a suite of single to quadruple knockout mutants with or without disruption. We tested these mutants for antiviral activities against diverse dsRNA viruses and ssRNA viruses. Although both DCL2 and AGL2 worked as antiviral players against some RNA viruses, DCL2 without argonaute was sufficient to block the replication of other RNA viruses. Overall, these results indicate the existence of a Dicer-alone defense and different degrees of susceptibility to it among RNA viruses. We discuss what determines the great difference in susceptibility to the Dicer-only defense.
抗病毒 RNA 干扰 (RNAi) 从酵母到哺乳动物都是保守的。Dicer 识别并切割病毒衍生的双链 RNA (dsRNA) 和/或结构的单链 RNA (ssRNA) 成小干扰 RNA,这些 RNA 引导效应 Argonaute 到同源病毒 RNA 进行消化,从而抑制病毒复制。因此,Argonaute 被认为是抗病毒 RNAi 所必需的。在这里,我们使用 (栗疫病菌) 展示了不依赖 Argonaute、依赖 Dicer 的抗病毒防御机制,该菌是一种丝状子囊菌模式真菌,宿主多种病毒。真菌有两个 Dicer 样基因 ( 和 ) 和四个 Argonaute 样基因 ( 到 )。我们制备了一系列单到四的 敲除突变体,有或没有 缺失。我们测试了这些突变体对不同 dsRNA 病毒和 ssRNA 病毒的抗病毒活性。虽然 DCL2 和 AGL2 都可以作为一些 RNA 病毒的抗病毒因子发挥作用,但没有 Argonaute 的 DCL2 足以阻止其他 RNA 病毒的复制。总的来说,这些结果表明存在一种 Dicer 单独的防御机制,并且不同的 RNA 病毒对其的敏感性程度不同。我们讨论了决定对 Dicer 唯一防御的敏感性差异的因素。