Development of second generation RNAi constructs against avian influenza virus

家禽不断接触各种各样的病毒，虽然它们对大多数病毒具有抵抗力，但也有少数病毒对它们造成伤害，疾病造成的经济损失占生产成本的10%至20%。最近的事件表明，鸡瘟(禽流感)是对世界家禽业的持续威胁。2003-2005年史无前例的疫情摧毁了东南亚的家禽业，最近不列颠哥伦比亚省爆发的禽流感表明，加拿大也不能幸免于这种疾病。禽流感不仅给家禽养殖业造成巨大的经济损失，而且对人类健康构成严重威胁。至少有222例人感染禽流感病毒，其中62人死亡，家禽养殖户、加工者及其家人受到不成比例的影响。此外，另一场全球流感大流行的可能性现在也被非常认真地对待。在禽流感暴发的第一个迹象出现时，必须销毁数百万只禽类，并实施从受影响国家进口家禽产品的禁运。几乎不可能消除野生候鸟体内禽流感病毒的自然储存，这些候鸟没有明显的症状，但很容易将致病病毒株传播到国外。由于流感病毒目标表位的快速抗原性漂移，疫苗接种仅有部分效果。常规育种没有产生高度抗性和商业上可接受的品种。由于病毒的传播依赖于宿主的细胞机制，因此阻止进入细胞内的这种机制可能会阻止病毒复制并中断感染周期。在本项目中，我们计划开发高效对抗禽流感病毒的RNAi分子。未来这项技术的发展可能会导致禽流感预防的开发和抗流感家禽的生产。这些研究的另一个重要好处是，它将使人们更好地了解自然RNAi在保护家禽免受病毒感染方面的作用。这一领域的进一步发展将使未来能够识别可能提高家禽对病毒感染抵抗力的等位基因。

Poultry is in continuous contact with a great variety of viruses, and while they are resistant to the majority of them, they are harmed by a few, with economic losses from diseases at 10 to 20% of the production cost. Recent events demonstrated that fowl plague (avian influenza) is a constant threat to worldwide poultry industry. The unprecedented epidemic of 2003-2005 decimated poultry industry in southeastern Asia, and recent outbreak of avian influenza in British Columbia demonstrated that Canada is not immune to the disease either. Avian influenza not only results in significant monetary loss for the poultry industry, but also represents a serious risk to human health. At least 222 cases of human infection by avian influenza virus with in 62 deaths, with poultry farmers, processors and their families been disproportionably affected. Also the possibility of another worldwide influenza pandemic is now taken very seriously. At the first sign of avian influenza outbreak, millions of birds have to be destroyed and an embargo on import of poultry products from the affected country is implemented. It is almost impossible to eliminate natural reservoirs of avian influenza virus in wild migratory birds that show no visible symptoms yet can easily spread the pathogenic virus strains across the borders. Vaccination is only partially effective due to rapid antigenic drift of targeted epitopes of influenza virus. Conventional breeding has not produced highly resistant and commercially acceptable varieties. As the virus depends on the host cellular machinery for its propagation, preventing access to this machinery in the cells might block viral replication and interrupt the infection cycle. In this project, we propose to develop RNAi molecules highly efficient against avian influenza virus. The development of this technology in the future might lead to development prophylactic for avian influenza, and production of influenza-resistant poultry. Another important benefit of these research is that it will allow better understanding the role of natural RNAi in protecting poultry from viral infection. Further development in this field will allow in the future to identify alleles which might increase resistance of poultry to viral infections.