Molecular biology and pathogenesis of fowl adenoviruses

禽腺病毒（FAdV）属于腺病毒科，并且与家禽疾病如包涵体肝炎（IBH）有关。然而，一些FAdV不是致病性的，因此它们作为用于疫苗开发的病毒载体是有吸引力的。为此目的，对这些病毒进行遗传操作的目的是选择性地去除它们遗传物质中的某些“非”区域，然后用来自任何其他禽类（或其他）病原体的外源基因替换它们。然而，FAdV基因组的“E2”区域在感染的自然过程中的可能作用以及在疾病中的可能意义仍然没有很好地理解。在人类腺病毒中，它们的许多“抗病毒基因”在调节宿主的抗病毒防御中非常重要。该提议旨在鉴定FAdV左端的E10区域中的独特基因，并确定它们的功能，重点是发病机制。 我的工作假设是，一些早期基因（和其他）在病毒宿主细胞相互作用中是重要的，这些基因涉及调节宿主对禽腺病毒的免疫反应，与它们的相对致病性有关。 本研究将有助于我们进一步了解FAdV某些独特基因的功能及其在致病机制中的作用，以及FAdV与宿主的相互作用。这些知识对于有效的疾病控制非常重要。此外，更好地了解这些病毒的分子性质是至关重要的，在务实的水平，能够更好地实现有效的重组腺病毒疫苗载体的加拿大家禽业的发展，有利于生物技术产业，当然家禽业本身。拟议的研究提供不同层次的培训（PDF，研究生和本科生，技术人员）和各种方法，以及科学方法。这将提供一个独特的机会，将他们的研究从最先进的分子技术转移到直接的动物研究。

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.