Development of second generation RNAi constructs against avian influenza virus

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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.