The unfolded protein response (UPR) is a cell-designated strategy that maintains the balance of protein folding in the endoplasmic reticulum (ER). UPR features a network of signal transduction pathways that reprogram the transcription, mRNA translation, and protein post-translational modification to relieve the ER stresses from unfolded/misfolded proteins. Infection with plant viruses can induce the UPR, and activated UPR often promotes plant viral infections in turn. However, the mechanism used by plant viruses to balance UPR and achieve robust infection remain largely unknown. In this study, P1SCSMV was identified as a virus-encoded RNA silencing suppressor (VSR). Heterologous overexpression of P1SCSMV via potato virus X (PVX) was found lead to programmed cell death (PCD) in Nicotiana benthamiana. Furthermore, P1SCSMV was also found to inhibit the PVX infection-triggered UPR by downregulating UPR-related genes and directly induced the distortion and collapse of the ER polygonal meshes on PVX-P1SCSMV infected N. benthamiana. Moreover, self-interaction, VSR activity, UPR inhibition, and cell death phenotype of P1SCSMV were also found to be dependent on its bipartite nuclear localization signal (NLS) (251RKRKLFPRIPLK262). P1SCSMV was found to directly bind to the stem-loop region of NbbZIP60U via its NLS and inhibit the UPR pathways, ultimately resulting in a PCD phenotype in PVX-P1SCSMV infected N. benthamiana leaves. This study also revealed the balancing role of potyviruses encoded P1SCSMV in the UPR pathway to achieve robust viral infection. This may represent a novel virulence strategy for plant viruses.

中文翻译：

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甘蔗条纹花叶病毒 P1 蛋白通过直接抑制 bZIP60U 剪接来抑制未折叠蛋白反应。

未折叠蛋白反应（UPR）是一种细胞指定的策略，可维持内质网（ER）中蛋白质折叠的平衡。UPR 具有信号转导通路网络，可重新编程转录、mRNA 翻译和蛋白质翻译后修饰，以缓解未折叠/错误折叠蛋白质造成的内质网应激。植物病毒感染可诱发UPR，而激活的UPR往往又反过来促进植物病毒感染。然而，植物病毒平衡UPR并实现强感染的机制仍然很大程度上未知。在这项研究中，P1SCSMV 被鉴定为病毒编码的 RNA 沉默抑制子 (VSR)。发现通过马铃薯病毒 X (PVX) 异源过度表达 P1SCSMV 会导致本塞姆氏烟草的程序性细胞死亡 (PCD)。此外，还发现P1SCSMV通过下调UPR相关基因来抑制PVX感染引发的UPR，并直接诱导PVX-P1SCSMV感染的本塞姆氏烟草的内质网多边形网格的扭曲和崩溃。此外，还发现 P1SCSMV 的自身相互作用、VSR 活性、UPR 抑制和细胞死亡表型依赖于其二分核定位信号 (NLS) (251RKRKLFPRIPLK262)。发现 P1SCSMV 通过 NLS 直接结合 NbbZIP60U 的茎环区域并抑制 UPR 途径，最终导致 PVX-P1SCSMV 感染的本塞姆氏烟草叶片出现 PCD 表型。这项研究还揭示了编码 P1SCSMV 的马铃薯病毒在 UPR 途径中的平衡作用，以实现强大的病毒感染。这可能代表了植物病毒的一种新的毒力策略。