Molecular biology and pathogenesis of fowl adenoviruses

禽腺病毒属于腺病毒科，与包涵体肝炎(IBH)等禽类疾病有关。然而，一些FAdv不是致病的，因此它们作为疫苗开发的病毒载体很有吸引力。为此，对这些病毒的基因操作旨在选择性地移除其遗传物质中的一些“可有可无”的区域，我已经确定了这些区域，然后用源自任何其他禽类(或其他)病原体的外来基因来替换它们。然而，FAdV基因组的“可有可无”区域在自然感染过程中的可能作用以及在疾病中的可能含义仍未被很好地了解。在人腺病毒中，它们的许多“可有可无的基因”在调节宿主的抗病毒防御方面非常重要。本研究的目的是鉴定FAdV左端可有区的独特基因，并确定其功能(S)，着重于发病机制。 我的工作假设是，一些可有可无的(和其他)早期基因在病毒宿主与细胞的相互作用中是重要的，而那些涉及调节宿主对禽腺病毒的免疫反应的基因与它们的相对致病性有关。 我的研究将加深我们对一些FAdV特有基因的功能及其在FAdV致病和FAdV与宿主相互作用中的作用的理解。这些知识对于有效的疾病控制很重要。此外，在实际层面上，更好地了解这些病毒的分子性质是至关重要的，以便能够更好地实现为加拿大家禽业开发有效的重组腺病毒疫苗载体，从而使生物技术行业受益，当然也有利于家禽业本身。拟议的研究提供不同级别的培训(PDF、研究生和本科生、技术人员)，并提供各种方法和科学方法的培训。这将提供独特的机会，将他们的研究从最先进的分子技术转移到直接在动物身上进行研究。

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.