Molecular Plant-Virus Interactions: Defense and Counter-defense

病毒病原体在新出现的植物疾病中所占比例最大，威胁着全球粮食安全。为了对抗病毒，植物进化出了复杂的防御机制。作为回应，病毒也进化出毒力策略来对抗宿主防御。我们研究计划的长期目标是了解复杂的病毒-植物相互作用，特别是病毒和植物之间的共同进化军备竞赛，以开发控制病毒疾病的新技术，以实现可持续的作物生产。越来越多的证据表明，RNA靶向免疫包括RNA沉默、RNA衰变和RNA质量控制，并调节内源基因表达，是植物对病毒病原体的中心防御。这些RNA免疫途径可能以层次化和协同的方式发挥作用，以RNA沉默为主要参与者来抑制病毒感染。RNA沉默，由双链RNA触发，是一种在所有真核生物中保守的基本的、序列特异性的机制。病毒编码RNA沉默的病毒抑制物(VSR)，它与细胞因子结合以应对RNA沉默。最近，我们发现VSR还通过与关键的细胞衰退途径成分相互作用来颠覆RNA的衰退，从而促进病毒感染，而自噬通过调节VSR在病毒感染中发挥着截然不同的作用(主要是抗病毒)。由于VSR在序列上高度多样化，它们似乎与宿主蛋白相互作用来执行其功能。在这项拟议的研究中，我们将识别通过与VSR相互作用而招募的宿主蛋白，这些蛋白专门用于RNA靶向的抗病毒免疫，而不是用于内源性基因调节。我们将进一步描述它们在抗性信号通路中的机制细节，并利用经典的、分子和高级细胞生物学技术阐明病毒如何干扰这些细胞因子的抗病毒功能。另一种新出现的重要的抗病毒防御是寄主因子介导的隐性抗性。绝大多数植物病毒都有一个小的正向单链RNA基因组，编码能力非常有限。因此，入侵的病毒依赖于许多宿主因子来建立其感染，而破坏宿主因子与病毒的相互作用会导致遗传抗性。在迄今已确定的多种宿主因子中，真核细胞翻译起始因子4E(EIF4E)或其亚型eIF(Iso)4E最为突出，因为eIF4E或eIF(Iso)4E的遗传损伤可能对许多病毒，特别是马铃薯Y病毒具有免疫力。不幸的是，潜在的机制仍然难以捉摸。最近，我们发现eIF4E介导的抗性可能与RNA靶向免疫相关。在这项拟议的研究中，我们还将利用遗传学、分子生物学和生化方法，从分子上了解eIF4E在病毒感染背景下的相互作用组，特别是RNA靶免疫在eIF4E介导的耐药性中的作用。

Viral pathogens account for the largest proportion of newly emerging plant diseases and threaten global food security. To combat viruses, plants have evolved sophisticated defense mechanisms. In response, viruses have also evolved virulence strategies to counteract host defense. The long-term goal of our research program is to understand the complex virus-plant interactions, in particular the co-evolutionary arms race between viruses and plants, for the development of novel technologies to control viral diseases for sustainable crop production. An increasing body of evidence suggests that RNA-targeted immunity, which embraces RNA silencing, RNA decay and RNA quality control and regulates endogenous gene expression, is a central defense to viral pathogens in plants. These RNA immunity pathways may act in a hierarchical and concerted mode to inhibit virus infection with RNA silencing as a master player. RNA silencing, triggered by double-stranded RNA, is a fundamental, sequence-specific mechanism conserved in all eukaryotes. Viruses encode viral suppressors of RNA silencing (VSRs) that bind to cellular factors to cope with RNA silencing. Recently, we have found that VSRs also subvert RNA decay through interactions with key cellular decay pathway components to promote viral infection and autophagy plays contrasting roles (predominantly antiviral) in virus infection by regulating VSRs. As VSRs are highly diverse in sequence, they appear to interact with host proteins to execute their function. In this proposed research, we will identify host proteins that are recruited via interactions with VSRs to function specifically for RNA-targeted antiviral immunity rather than for endogenous gene regulation. We will further characterize their mechanistic details in the resistance-signaling pathway and elucidate how viruses interfere the antiviral function of these cellular factors using classical, molecular and cell biology techniques. Another emerging crucial antiviral defense is host factor-mediated recessive resistance. The vast majority of plant viruses have a small positive-sense, single-stranded RNA genome with very limited coding capacity. Thus, the invading virus depends on a number of host factors to establish its infection and disruption of the host factor-virus interaction leads to genetic resistance. Among a number of host factors identified so far, the eukaryotic translation initiation factor 4E (eIF4E) or its isoform eIF(iso)4E is outstanding as genetic lesions of eIF4E or eIF(iso)4E may confer immunity to a number of viruses, particularly potyviruses. Unfortunately, the underlying mechanism still remains elusive. Recently, we have found that eIF4E-mediated resistance may interlink with RNA-targeted immunity. In this proposed research, we will also molecularly understand and functionally characterize the eIF4E interactome in the context of virus infection, particularly the role of RNA-target immunity in eIF4E-mediated resistance using genetic, molecular and biochemical approaches.