London Research and Development Centre, Agriculture and Agri-Food Canada, London, ON, N5V 4T3, Canada.
Department of Biology, Western University, London, ON, N6A 5B7, Canada.
Nat Commun. 2018 Mar 28;9(1):1268. doi: 10.1038/s41467-018-03658-2.
Autophagy emerges as an essential immunity defense against intracellular pathogens. Here we report that turnip mosaic virus (TuMV) infection activates autophagy in plants and that Beclin1 (ATG6), a core component of autophagy, inhibits virus replication. Beclin1 interacts with NIb, the RNA-dependent RNA polymerase (RdRp) of TuMV, via the highly conserved GDD motif and the interaction complex is targeted for autophagic degradation likely through the adaptor protein ATG8a. Beclin1-mediated NIb degradation is inhibited by autophagy inhibitors. Deficiency of Beclin1 or ATG8a enhances NIb accumulation and promotes viral infection and vice versa. These data suggest that Beclin1 may be a selective autophagy receptor. Overexpression of a Beclin1 truncation mutant that binds to NIb but lacks the ability to mediate NIb degradation also inhibits virus replication. The Beclin1-RdRp interaction further extends to several RNA viruses. Thus Beclin1 restricts viral infection through suppression and also likely autophagic degradation of the viral RdRp.
自噬作为一种重要的免疫防御机制，可对抗细胞内病原体。在这里，我们报告芜菁花叶病毒（TuMV）感染可激活植物中的自噬，并且自噬的核心组成部分 Beclin1（ATG6）可抑制病毒复制。Beclin1 通过高度保守的 GDD 基序与 TuMV 的 RNA 依赖性 RNA 聚合酶（RdRp）NIb 相互作用，并且该相互作用复合物可能通过衔接蛋白 ATG8a 被靶向进行自噬降解。自噬抑制剂抑制 Beclin1 介导的 NIb 降解。Beclin1 或 ATG8a 的缺乏会促进 NIb 的积累，从而促进病毒感染，反之亦然。这些数据表明 Beclin1 可能是一种选择性自噬受体。过表达与 NIb 结合但缺乏介导 NIb 降解能力的 Beclin1 截断突变体也可抑制病毒复制。Beclin1-RdRp 相互作用进一步扩展到几种 RNA 病毒。因此，Beclin1 通过抑制以及可能通过自噬降解病毒 RdRp 来限制病毒感染。
