Host factors controlling foot-and-mouth disease virus (FMDV) replication: towards genetic control of FMD in pigs

控制口蹄疫病毒（FMDV）复制的宿主因素：猪口蹄疫的遗传控制

• 批准号: BB/T003138/1
• 负责人: Tobias Tuthill
• 金额: $ 91.41万
• 依托单位: The Pirbright Institute
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FT003138%2F1
• 关键词: Host; factors; controlling; foot; mouth

One of the world's biggest challenges is to meet a growing demand for food. Pork is the most widely consumed meat and the world's largest source of animal protein. Foot-and-mouth disease virus (FMDV) causes an economically devastating disease of pigs and other livestock and affects both the developed and developing world. Therefore improved control of FMD in pigs could sustainably improve the performance of global livestock industries and have enormous economic and social value worldwide especially in developing regions such as parts of Asia with rapidly growing demand for pork. FMD vaccines are available and often used to help control the disease in cattle, however such vaccines have limited effectiveness in pigs. Genetic engineering of animals for disease resistance is a potential alternative strategy for preventing FMD in livestock species. Such engineering is now possible in the domestic pig, as demonstrated by the recent production of gene-edited pigs which are resistant to another unrelated viral pathogen, porcine reproductive and respiratory syndrome virus (PRRSV). Unlike transgenic approaches, gene editing does not add foreign genetic material and this distinction has already allowed gene-edited plants to be used for food production in some regions of the world.For viruses to replicate inside host cells, they must interact with various host proteins which are in turn encoded by specific genes in the host genome. Genes identified as essential for virus replication but non-essential for normal host phenotype, can be modified or made non-functional so that the virus can no longer replicate. We have preliminary data showing that such genes can be identified in pig cells and that reducing expression of these genes does indeed prevent virus replication. We now wish to i) expand the search for these genes using techniques tailored to the porcine genome, ii) obtain proof-of-principle that disrupting gene expression will prevent FMD in animals using mouse models and iii) generate engineered cell lines to understand how best to prevent viral replication by gene editing of the porcine genome. We believe the outcomes of the proposed study will provide the information required to begin genetic engineering of the pig for resistance to FMD.

世界面临的最大挑战之一是满足日益增长的粮食需求。猪肉是消费最广泛的肉类，也是世界上最大的动物蛋白来源。口蹄疫病毒（FMDV）导致猪和其他牲畜的经济破坏性疾病，影响发达国家和发展中国家。因此，改善对猪口蹄疫的控制可以可持续地改善全球畜牧业的表现，并在全球范围内具有巨大的经济和社会价值，特别是在发展中地区，如对猪肉需求迅速增长的亚洲部分地区。口蹄疫疫苗是可用的，通常用于帮助控制牛的疾病，但这种疫苗对猪的有效性有限。动物抗病基因工程是预防家畜口蹄疫的一种潜在的替代策略。这种工程现在可以在家猪中进行，最近生产的基因编辑猪对另一种不相关的病毒病原体猪繁殖与呼吸综合征病毒（PRRSV）具有抗性。与转基因方法不同，基因编辑不会添加外源遗传物质，这一区别已经允许基因编辑的植物在世界某些地区用于食品生产。对于病毒在宿主细胞内复制，它们必须与各种宿主蛋白相互作用，这些蛋白又由宿主基因组中的特定基因编码。被鉴定为病毒复制所必需但对正常宿主表型非必需的基因可以被修饰或使其无功能，使得病毒不能再复制。我们有初步的数据表明，这些基因可以在猪细胞中被识别出来，减少这些基因的表达确实可以阻止病毒的复制。我们现在希望i）使用针对猪基因组定制的技术来扩大对这些基因的搜索，ii）使用小鼠模型获得破坏基因表达将防止动物中的FMD的原理证明，以及iii）产生工程化细胞系以了解如何通过猪基因组的基因编辑来最好地防止病毒复制。我们相信，拟议的研究结果将提供所需的信息，开始基因工程的猪抵抗口蹄疫。

项目成果

A Methodology for Remote Microwave Sterilization Applicable to the Coronavirus and Other Pathogens Using Retrodirective Antenna Arrays.

• DOI: 10.1109/jerm.2021.3077110
• 发表时间: 2022-03
• 期刊: IEEE journal of electromagnetics, RF and microwaves in medicine and biology
• 作者: Kossenas K;Podilchak SK;Comite D;Re PDH;Goussetis G;Pavuluri SK;Griffiths SJ;Chadwick RJ;Guo C;Bruns N;Tait-Burkard C;Haas JG;Desmulliez MPY
• 通讯作者: Desmulliez MPY