Molecular Plant-Virus Interactions: Defense and Counter-defense

分子植物-病毒相互作用：防御与反防御

• 批准号: RGPIN-2020-06416
• 负责人: Wang, Aiming
• 金额: $ 4.23万
• 依托单位: University of Western Ontario
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=745931
• 关键词: Molecular; Plant; Virus; Interactions; Defense

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.

病毒病原体在新出现的植物病害中所占比例最大，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，病毒也进化出了毒性策略来抵消宿主的防御。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，以开发新技术来控制病毒性疾病，实现可持续的作物生产。越来越多的证据表明，RNA靶向免疫是植物对病毒病原体的核心防御，它包括RNA沉默、RNA降解和RNA质量控制，并调节内源基因的表达。这些RNA免疫途径可能以分级和协调的模式发挥作用，以RNA沉默作为主要参与者来抑制病毒感染。由双链RNA触发的RNA沉默是所有真核生物中保守的基本的序列特异性机制。病毒编码RNA沉默的病毒抑制子（VSR），其结合细胞因子以科普RNA沉默。最近，我们发现VSR还通过与关键细胞衰变途径组分相互作用来破坏RNA衰变以促进病毒感染，而自噬通过调节VSR在病毒感染中发挥相反的作用（主要是抗病毒）。由于VSR序列高度多样，它们似乎与宿主蛋白相互作用以执行其功能。在这项拟议的研究中，我们将确定通过与VSR相互作用招募的宿主蛋白质，这些蛋白质专门用于RNA靶向的抗病毒免疫，而不是内源性基因调控。我们将使用经典、分子和细胞生物学技术进一步表征它们在耐药信号通路中的机制细节，并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抗病毒防御是宿主因子介导的隐性抗性。绝大多数植物病毒具有编码能力非常有限的小的正义单链RNA基因组。因此，入侵病毒依赖于许多宿主因子来建立其感染，并且宿主因子-病毒相互作用的破坏导致遗传抗性。在迄今为止鉴定的许多宿主因子中，真核翻译起始因子4 E（eIF 4 E）或其同种型eIF（iso）4 E是突出的，因为eIF 4 E或eIF（iso）4 E的遗传损伤可赋予对许多病毒（特别是马铃薯Y病毒）的免疫性。不幸的是，根本的机制仍然难以捉摸。最近，我们发现eIF 4 E介导的抗性可能与RNA靶向免疫相互关联。在这项拟议的研究中，我们还将从分子上了解和功能上表征病毒感染背景下的eIF 4 E相互作用组，特别是RNA靶向免疫在eIF 4 E介导的抗性中的作用，使用遗传，分子和生物化学方法。