Deciphering the enigmatic expression mechanism of the newly discovered PIPO gene in the Potyviridae family of plant viruses

破译马铃薯病毒科植物病毒中新发现的PIPO基因的神秘表达机制

• 批准号: BB/J015652/1
• 负责人: Andrew Firth
• 金额: $ 43.92万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FJ015652%2F1
• 关键词: Deciphering; enigmatic; expression; mechanism; newly

Plant viruses are one of the major causes of crop loss world-wide, with revenue lost due to reduced yield amounting to some US$60 billion annually. Revenue is also lost due to the implementation of costly control strategies (e.g. chemical control of insects that transmit viruses between host plants, destruction of infected orchards). More importantly, virus-induced crop failure exacerbates famine and ruins livelihoods in developing nations and communities that rely on subsistence farming. Thus, providing effective control measures for plant viral diseases is a crucial component of strategies for maintaining food security both in the UK and worldwide. This is particularly important, now, as populations continue to expand and natural resources including arable land are further depleted.The largest and most economically important group of plant viruses are the potyviruses. This virus family encompasses almost a third of known plant virus species and is responsible for around half of viral crop damage worldwide. Potyviruses that are of great agricultural significance include potato viruses Y and A, turnip mosaic virus, soybean mosaic virus, sweet potato feathery mottle virus, zucchini yellow mosaic virus, papaya ringspot virus, and plum pox virus. Plum pox, for example, is considered the most devastating viral disease of stone-fruit species such as plum and apricot (estimated costs amounting to 10 billion euro over 30 years). Turnip mosaic virus is particularly important in the UK and worldwide, infecting a huge variety of crops including many brassicas (oilseed rape, cabbage, cauliflower, turnip etc), lettuce, courgette, rhubarb and radish. Meanwhile, sweet potato feathery mottle potyvirus presents a dire threat to food security in sub-Saharan Africa.We are interested in the mechanisms by which viruses replicate and spread within plants - a drama that unfolds at the molecular level. The central 'dogma' of molecular biology, articulated by Nobel Laureate Francis Crick in 1958, describes the transfer of information between the three major classes of information-carrying biological chemicals: genetic information passes from one generation to the next via the replication of DNA and, within an organism, genes encoded within the DNA genome are 'transcribed' into 'messenger' RNA molecules that are used ('translated') to direct the synthesis of proteins. The roles of DNA and RNA are predominantly as carriers of genetic information, while proteins can have varied roles, for example catalyzing important chemical reactions ('enzymes'), or helping to form the architecture of the cell and its contents. Remarkably, however, most plant viruses, have tiny genomes that are made up of RNA instead of DNA. In most cases, the RNA genome serves directly as a messenger RNA for translation of the viral proteins by pirating the host cell's protein synthesis machinery. Some of these virus proteins are enzymes that the virus uses to replicate its genome, while other virus proteins are used to make the protective capsids that protect the viral genome as it is ferried from one host to another.Because most plant virus genomes serve directly as messenger RNAs, plant viruses have evolved a variety of unusual mechanisms for controlling gene expression at the level of protein translation. Some of these mechanisms are extraordinarily different from mechanisms used by host plant genes, and are therefore potential targets for virus control strategies. We aim to decipher a completely new and unsuspected translational mechanism that we recently discovered in the potyviruses. The translational mechanism is essential for potyvirus infectivity, but appears to involve completely novel mechanisms, that are not known to be used by any other virus or organism. By figuring out this mechanism, we hope to learn new ways of sustainably controlling potyviruses. We also hope to learn new mechanisms for controlling gene expression that will be useful in biotechnology.

植物病毒是世界范围内作物损失的主要原因之一，每年因减产造成的收入损失约为600亿美元。由于实施代价高昂的控制战略（例如，对在寄主植物之间传播病毒的昆虫进行化学控制、摧毁受感染的果园），也造成了收入损失。更重要的是，病毒导致的作物歉收加剧了饥荒，破坏了依赖自给农业的发展中国家和社区的生计。因此，为植物病毒性疾病提供有效的控制措施是维持英国和全世界粮食安全战略的重要组成部分。在人口继续扩大和包括可耕地在内的自然资源进一步枯竭的今天，这一点尤其重要。最大和经济上最重要的一类植物病毒是多型病毒。该病毒家族包含了已知植物病毒种类的近三分之一，并对全球约一半的病毒性作物损害负责。具有重要农业意义的痘病毒包括马铃薯病毒Y和A、萝卜花叶病毒、大豆花叶病毒、甘薯羽毛斑驳病毒、西葫芦黄花叶病毒、木瓜环斑病毒和李子痘病毒。例如，梅痘被认为是李子和杏等核果物种中最具破坏性的病毒性疾病（估计在30年内造成的损失达100亿欧元）。芜菁花叶病毒在英国和世界范围内尤为重要，感染多种作物，包括许多芸苔属植物（油菜、卷心菜、花椰菜、萝卜等）、生菜、小胡瓜、大黄和萝卜。与此同时，甘薯羽状斑驳病毒对撒哈拉以南非洲的粮食安全构成了严重威胁。我们对病毒在植物内复制和传播的机制很感兴趣——这是一出在分子水平上展开的戏剧。1958年，诺贝尔奖得主弗朗西斯·克里克（Francis Crick）阐述了分子生物学的核心“教条”，描述了三种主要携带信息的生物化学物质之间的信息传递：遗传信息通过DNA的复制从一代传递到下一代，在生物体中，DNA基因组内编码的基因被“转录”成“信使”RNA分子，这些RNA分子被用来（“翻译”）指导蛋白质的合成。DNA和RNA的作用主要是作为遗传信息的载体，而蛋白质可以有不同的作用，例如催化重要的化学反应（“酶”），或帮助形成细胞及其内容物的结构。然而，值得注意的是，大多数植物病毒都有由RNA而不是DNA组成的微小基因组。在大多数情况下，RNA基因组通过窃取宿主细胞的蛋白质合成机制，直接充当翻译病毒蛋白质的信使RNA。其中一些病毒蛋白是病毒用于复制其基因组的酶，而其他病毒蛋白则用于制造保护性衣壳，在病毒基因组从一个宿主转移到另一个宿主时保护病毒基因组。由于大多数植物病毒基因组直接作为信使rna，植物病毒已经进化出多种不同寻常的机制来控制蛋白质翻译水平上的基因表达。其中一些机制与寄主植物基因使用的机制截然不同，因此是病毒控制策略的潜在目标。我们的目标是破译一种全新的、意想不到的翻译机制，这是我们最近在波蒂病毒中发现的。这种转译机制对痘病毒的传染性至关重要，但似乎涉及到一种全新的机制，这种机制尚不为其他任何病毒或生物体所知。通过弄清这一机制，我们希望找到可持续控制痘病毒的新方法。我们也希望了解控制基因表达的新机制，这将在生物技术中有用。

项目成果

The Rumsfeld paradox: some of the things we know that we don't know about plant virus infection.

拉姆斯菲尔德悖论：关于植物病毒感染，我们知道一些我们不知道的事情。

• DOI: 10.1016/j.pbi.2013.06.004
• 发表时间: 2013
• 期刊: Current opinion in plant biology
• 影响因子: 9.5
• 作者: Palukaitis P

Novel virus discovery and genome reconstruction from field RNA samples reveals highly divergent viruses in dipteran hosts.

• DOI: 10.1371/journal.pone.0080720
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Cook S;Chung BY;Bass D;Moureau G;Tang S;McAlister E;Culverwell CL;Glücksman E;Wang H;Brown TD;Gould EA;Harbach RE;de Lamballerie X;Firth AE
• 通讯作者: Firth AE

Mutational analysis of the Potyviridae transcriptional slippage site utilized for expression of the P3N-PIPO and P1N-PISPO proteins.

• DOI: 10.1093/nar/gkw441
• 发表时间: 2016-09-19
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Olspert A;Carr JP;Firth AE
• 通讯作者: Firth AE

Transcriptional slippage in the positive-sense RNA virus family Potyviridae.

阳性RNA病毒家族波托病毒科中的转录滑动。

• DOI: 10.15252/embr.201540509
• 发表时间: 2015-08
• 期刊: EMBO reports
• 影响因子: 7.7
• 作者: Olspert A;Chung BY;Atkins JF;Carr JP;Firth AE
• 通讯作者: Firth AE

Discovery of a Small Non-AUG-Initiated ORF in Poleroviruses and Luteoviruses That Is Required for Long-Distance Movement.

• DOI: 10.1371/journal.ppat.1004868
• 发表时间: 2015-05
• 期刊: PLoS pathogens
• 影响因子: 6.7
• 作者: Smirnova E;Firth AE;Miller WA;Scheidecker D;Brault V;Reinbold C;Rakotondrafara AM;Chung BY;Ziegler-Graff V
• 通讯作者: Ziegler-Graff V