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，但它们受到少数病毒的伤害，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，家禽鼠疫（禽流感）对世界范围内的家禽业是一个持续的威胁。2003-2005年前所未有的流行病摧毁了东南亚的家禽业，最近在不列颠哥伦比亚省爆发的禽流感表明，加拿大也不能对这种疾病免疫。禽流感不仅给家禽业造成重大经济损失，而且对人类健康构成严重威胁。至少有222人感染禽流感病毒，其中62人死亡，家禽养殖户、加工商及其家庭受到不成比例的影响。此外，现在非常重视再次发生全球流感大流行的可能性。在禽流感爆发的第一个迹象，数以百万计的家禽必须被销毁，并对从受影响国家进口家禽产品实行禁运。几乎不可能消除野生候鸟中禽流感病毒的天然宿主，这些候鸟没有明显症状，但很容易将致病性病毒株跨国界传播。由于流感病毒的目标抗原表位快速漂移，疫苗接种仅部分有效。传统育种尚未产生高抗性和商业上可接受的品种。由于病毒的繁殖依赖于宿主的细胞机制，因此在细胞中阻止这种机制可能会阻止病毒复制并中断感染周期。本课题拟开发高效抗禽流感病毒的RNAi分子。未来这项技术的发展可能会导致禽流感预防措施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天然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将来能够确定可能增加家禽对病毒感染的抗性的等位基因。

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.