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

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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.