Unravelling the aetiology of Stunting in UK Broiler Flocks through the use of novel microdissection and viral meta-transcriptomic sequencing tools

通过使用新型显微解剖和病毒宏转录组测序工具揭示英国肉鸡群发育迟缓的病因

• 批准号: BB/X01732X/1
• 负责人: Victoria Smyth
• 金额: $ 64.41万
• 依托单位: Agri Food and Biosciences Institute
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FX01732X%2F1
• 关键词: Unravelling; aetiology; Stunting; UK; Broiler

The challenge addressed by this project is to unravel the causes of stunting disease in UK broiler chickens. Stunting syndrome has been a production issue in commercial broiler flocks since they became industrialised after the second world war, but is also a problem for small producers in low and middle income countries, such as Nigeria, where women often raise small numbers of chickens to supplement the family income. The stunting problem has many names, including infectious stunting, runting stunting syndrome and malabsorption disease. It pertains to a failure to grow properly despite sufficient feed. Birds typically present with stunting problems around the second to third week post hatching, but clinical signs may be observable earlier. As well as the reduction in weight gain, which can be substantial with severely affected chickens only a fraction of their potential weight for age, there may be other signs such as altered appetite, watery droppings, abnormal feathering and enteritis. We and other groups have evidence that the stunting is caused by infectious agents: chiefly, viral aetiology is suspected and experimental infections at AFBI using specific strains of the endemic, enteric viruses, astroviruses and reoviruses separately have resulted in some of the signs observed during stunting, e.g. weight loss or lesions in the gut mucosa. Other groups have also demonstrated some of the signs of stunting from inoculating birds with single viral strains of these and other viral candidates, e.g. birnavirus; however, none have fully recreated the stunting syndrome, and co-infections with more than one viral agent are considered the more probable aetiology. Moreover, diverse strains of these viruses are in circulation which are known to vary widely in pathogenicity with the majority potentially of low or no pathogenicity and accordingly high levels of these virus may be detected in young, healthy, unaffected birds. Other confounding factors in attributing disease aetiology includes the presence of maternally-derived antibodies, route of transmission (from the hen versus their environment) and the age at which birds become infected, since increasing age appears to confer resistance. All these factors have also hampered the identification of the virus(es) responsible for stunting diseases.The specific aims of the proposal are to: 1) identify a virus or viruses that are actively replicating within the lesions associated with stunting disease and that are present in many similar lesions from clinical cases. Histopathology and laser microdissection will identify and excise lesions from which nucleic acids will be sequenced to determine which virus strain(s) is present at levels indicative of an active infection. 2) confirm that the virus or viruses identified are aetiological agents of stunting; firstly, by cellular and tissue-based methods in the laboratory and secondly, by challenge studies of healthy chickens using purified isolates of the identified virus(es), which will demonstrate the development of hallmark lesions and associated clinical signs typical of stunting disease. These objectives will be achieved through the use of state of the art imaging and genomic methodologies, and through collaboration with the Industry (Moy Park, which is one of UK's top broiler meat producers and St David's Poultry Team, the leading poultry veterinary practice in the country).Currently there are no commercial vaccines to prevent stunting or specific treatments for affected flocks so that affected birds are culled. The results of this project will provide evidence of the causal agents of stunting that will enable improved diagnostics and potential interventions for veterinarians, and for vaccine companies to develop appropriate vaccines.

该项目所面临的挑战是解开英国肉鸡发育迟缓疾病的原因。自第二次世界大战后工业化以来，发育迟缓综合征一直是商业肉鸡群的生产问题，但也是低收入和中等收入国家（如尼日利亚）小生产者的问题，其中妇女经常饲养少量鸡以补充家庭收入。发育迟缓问题有许多名称，包括传染性发育迟缓、发育迟缓综合征和吸收不良疾病。它涉及到尽管有足够的饲料，但不能正常生长。鸟类通常在孵化后第二至第三周出现发育迟缓问题，但临床症状可能会更早观察到。除了体重增加的减少，严重受影响的鸡只可能是其年龄潜在体重的一小部分，可能还有其他迹象，如食欲改变，水样粪便，羽毛异常和肠炎。我们和其他研究小组有证据表明，发育迟缓是由感染因子引起的：主要是怀疑病毒病因，AFBI分别使用地方性肠道病毒、星状病毒和呼肠孤病毒的特定毒株进行实验性感染，导致发育迟缓期间观察到的一些体征，例如体重减轻或肠粘膜病变。其他研究小组也证实了这些病毒和其他候选病毒（例如双RNA病毒）的单一病毒株导致的一些鸟类发育迟缓的迹象;然而，没有一个病毒株完全重现了发育迟缓综合征，并且与一种以上病毒因子的合并感染被认为是更可能的病因。此外，这些病毒的不同毒株在流通中，已知其致病性差异很大，大多数可能具有低致病性或无致病性，因此在年轻、健康、未受影响的鸟类中可能检测到高水平的这些病毒。归因于疾病病因的其他混杂因素包括存在母体来源的抗体、传播途径（来自母鸡与其环境）和禽类感染的年龄，因为年龄的增加似乎会产生耐药性。所有这些因素也阻碍了对导致发育迟缓疾病的病毒的鉴定，该提案的具体目标是：1）鉴定在与发育迟缓疾病相关的病变内活跃复制的病毒，以及存在于临床病例的许多类似病变中的病毒。组织学和激光显微切割将识别和切除病变，从这些病变中进行核酸测序，以确定哪种病毒株以指示活动性感染的水平存在。2)确认所鉴定的病毒是发育迟缓的病原体;首先，通过实验室中基于细胞和组织的方法，其次，通过使用所鉴定病毒的纯化分离株对健康鸡进行攻毒研究，这将证明发育迟缓病的典型标志性病变和相关临床体征的发展。这些目标将通过使用最先进的成像和基因组方法，并通过与业界（Moy Park，英国最大的肉鸡生产商之一和St大卫家禽团队，该国领先的家禽兽医实践）的合作来实现。目前还没有商业疫苗来预防发育迟缓或对受影响的鸡群进行特定治疗，以便剔除受影响的鸟类。该项目的结果将为发育迟缓的病因提供证据，从而改善兽医的诊断和可能的干预措施，并使疫苗公司能够开发适当的疫苗。