Restriction of avian viruses by host interferon-inducible transmembrane proteins (IFITMs).

家禽产品是全世界供人类食用的动物蛋白的主要来源。目前全球每年生产550亿只鸡。全球人口增长和日益富裕正在推动对禽肉和禽蛋的需求，并且需要增加其供应。英国家禽业为英国经济贡献了约34亿英镑。感染家禽的病毒通过丧失生产力和疾病对动物健康构成重大挑战。通过减少禽肉和禽蛋的产量，这些因素同时对全球家禽业产生影响。鸟类通常在没有任何临床症状的情况下携带病毒；然而，某些类型的病毒在家禽中引起严重疾病，造成巨大的动物福利和经济成本。因此，制定针对这些病毒性疾病的有效控制战略对家禽业至关重要，而且对减轻发展中国家的贫困也非常重要，这些疾病在发展中国家广泛传播，对家禽养殖造成毁灭性影响。最近的证据显示，人类细胞中产生的一个蛋白质家族能够限制几种非常危险的人类病毒的进入过程和复制。这些蛋白参与病毒性疾病的直接临床相关性最近已在因季节性流感病毒住院的患者中得到证实。在这项研究中，研究人员发现，更多有严重症状的患者体内有一种特殊的蛋白质，这种蛋白质在人群中并不常见。这些结果表明，这些蛋白质的作用可以通过限制病毒在人体细胞中的传播来深刻地改变流感感染的过程。尽管这些蛋白质在人类和小鼠中已经被很好地表征，但在其他物种中却很少有数据存在。迄今为止，在鸡身上只发表了两种这样的蛋白质的有限细节；被认为相当于五种已知人类蛋白质中的两种。目前还没有对这些鸡蛋白在控制禽流感病毒中所起的作用进行描述。由于这些蛋白质似乎是抵御感染的第一道防线，这表明具有更活跃的蛋白质版本的单个鸡或整个家禽群可能对禽流感病毒和其他致病性家禽病毒性疾病具有更强的抵抗力。这项提案中提出的研究将在解释基因和蛋白质如何与鸡的病毒易感性联系起来方面发挥重要作用。我们提出这一建议的初步工作已经确定，鸡确实有类似的这些蛋白质，它们可以预防流感感染。影响这些蛋白质的变异，正如在人类群体中看到的那样，解释了为什么一些鸟类更容易受到病毒感染，这是非常可信的。通过分析对这些病毒的抗性水平不同的鸟类的遗传物质，我们希望确定在实验室和商业鸡中提供保护的这些蛋白质的鸡版本。对鸡中这些蛋白质的分析不仅为更好地了解病毒耐药性的增加提供了机会，而且还为家禽业提供了对抗病毒的工具。有选择地培育对病毒感染有更好抵抗力的鸟类可能是可行的；然而，这需要确定与抗性相关的因素并了解它们如何起作用。因此，这项建议的目的是了解鸡的生物学和这些基因的任何遗传变化。具体来说，我们将检验这些基因保护鸡免受病毒侵害的能力。这个项目的成果将是鉴定这些对许多禽流感病毒具有抵抗力的蛋白质的不同版本。家禽育种公司将能够在未来的所有育种计划中选择编码这些蛋白质的基因的保护性版本。

Poultry products are the main source of animal protein for human consumption worldwide. Current global production is 55 billion chickens per year. Global population growth and rising affluence are fuelling demand for poultry meat and eggs, and a need exists to increase their supply. The UK poultry industry contributes around £3.4bn to the UK economy. Viruses that infect poultry create major challenges to animal health through loss of productivity and disease. These have simultaneous effects on the global poultry industry through a reduction in the output of poultry meat and eggs. Birds often carry viruses in the absence of any clinical symptoms; however some types of viruses cause severe diseases in poultry that exert substantial animal welfare and economic costs. Therefore, developing efficient control strategies against these viral diseases is crucial for the poultry industry, but also very important in alleviating poverty in developing countries, where these diseases are widespread, causing devastating effects on poultry farming. Recent evidence has revealed that a family of proteins produced in human cells is able to limit the entry processes and replication of several very dangerous human viruses. Direct clinical relevance of the involvement of these proteins in viral diseases has recently been shown in patients hospitalized with the seasonal flu viruses. In this study researchers showed that more patients with severe symptoms had a particular version of the protein that is not commonly found in the population. These results reveal that the action of these proteins can profoundly alter the course of flu infections by limiting the spread of virus in the body's cells. Although these proteins have been well characterised in human and mouse, little data exists for other species. To date only limited details of two such proteins have been published in chickens; thought to be equivalent to two of the five known human proteins. No characterisation has been undertaken of the role that these chicken proteins play in the control of avian viruses. Since these proteins appear to be the first line of defence against infection, this suggests that individual chickens or entire poultry flocks with more active versions of the protein may be more resistant to avian influenza virus and other pathogenic poultry viral diseases. The research set out in this proposal will play a fundamental part in explaining how both the gene and protein are linked to viral susceptibility in chickens. Our preliminary work leading to this proposal has established that chickens do indeed have similar version of these proteins, and that they can protect against influenza infection.It is highly plausible that variation affecting these proteins, as is seen in the human population, explains why some birds are more susceptible to viral infections. By analysing the genetic material of birds that differ in levels of resistance to these viruses, we hope to identify the chicken versions of these proteins that give protection, both in laboratory and commercial chickens. Analysis of these proteins in the chicken presents opportunities not just for a greater understanding of increased viral resistance, but also as tools to combat viruses in the poultry industry. It may be feasible to selectively breed for birds with improved resilience to viral infections; however this requires the identification of resistance-associated factors and knowledge of how they act. The aim of this proposal is therefore to understand the biology and any genetic changes of these genes in chickens. Specifically we will examine the ability of the genes to protect the chickens against viruses. The output of this project will be in identifying versions of these proteins that give resistance to a number of avian viruses. Poultry breeding companies will then be able to select the protective version of the genes encoding these proteins in all future breeding programmes.