Molecular biology and pathogenesis of fowl adenoviruses

点击翻译按钮获取中文摘要

Fowl adenoviruses (FAdVs) are in the family Adenoviridae, and are implicated in diseases of poultry such as inclusion body hepatitis (IBH). However, some FAdVs are not pathogenic and therefore they are attractive as viral vectors for vaccine development. For this purpose, genetic manipulation of these viruses is directed towards the selective removal of some "dispensable" regions of their genetic material, which I have already identified, followed by their replacement with foreign genes originating from any other avian (or other) pathogens. However the possible roles of the "dispensable" regions of FAdV genomes in the natural course of infection and the probable implications in disease are still not well understood. In human adenovirus many of their "dispensable genes" are very important in modulating the host's antiviral defense. This proposal is aimed to identify the FAdV unique genes in the dispensable region at the left end and to determine their function(s) with an emphasis on pathogenesis. My working hypothesis is that some of the dispensable (and other) early genes are important in virus host-cell interaction and that those genes implicated in modulating the host's immune responses against fowl adenoviruses relate to their relative pathogenicity. My research will increase our understanding of the functions of some FAdV unique genes and their role in pathogenesis and the interaction of FAdVs with their host. This knowledge is important for effective disease control. Moreover, a better understanding of the molecular nature of these viruses is of paramount importance at a pragmatic level to be able to better realize the development of effective recombinant adenovirus vaccine vectors for Canada's poultry industry, benefiting the biotechnology industry and certainly the poultry industry itself. The proposed research provides training at different levels (PDF, graduate and undergraduate students, technicians) and in a variety of methodologies, and the scientific approach. This will provide the unique opportunity to move their research from state-of-the-art molecular techniques to direct studies in animals.