Biology of fowl adenoviruses

禽类卫生，包括防止感染病原体，是可靠地向世界大部分人口提供这种主食来源的安全供应的重要组成部分。尽管传染因子不同，但鸟类和人类一样容易感染传染病。最近在东南亚和欧洲暴发的H5N1禽流感病毒就有力地说明了这一点。类似地，2004年加拿大西部爆发了H7N3型流感病毒，导致许多禽类死亡，更多的禽类被扑杀。这些疾病不仅直接影响到养鸡业，而且还影响到这种食品供应的可靠性。在我的研究中，我研究了几种禽病毒性疾病，目的是能够更好地了解它们，为检测它们提供诊断工具，并开发疫苗或抗病毒策略，以更好地保护鸟类免受这些疾病的侵害。在目前的建议和我最近的研究中，我把重点放在了一组主要感染鸡的病毒，称为禽腺病毒（FAdVs）。虽然一些FAdVs感染似乎无症状，但其他FAdVs具有高致死率的高毒性，并且一些FAdVs似乎损害了免疫系统抵抗其他微生物病原体感染的能力。我的研究已经揭示了鸟类与哺乳动物腺病毒基因组成的主要差异，我相信这些鸟类腺病毒的差异与它们与鸟类宿主的特定相互作用直接相关，其中一些是导致不同的fadv对受感染鸟类产生生物效应的原因。为了确定哪些基因负责宿主病毒复制和病理的各个方面，我开发了一个简单的（FAdmid）系统，在这个系统中，我可以删除一个完整的基因或改变它。使用这种方法，我将生成一组FAdV特有的各种基因缺陷的突变体，并测试这些突变体对病毒复制的影响，首先在细胞培养中确定哪些基因对病毒复制至关重要，然后在鸡中监测感染野生型（未改变）病毒与突变型病毒的鸟类在发病机制和免疫反应方面的差异。

Avian health, including protection from infectious agents, is an important component of reliably providing much of the world's population a safe supply of this staple food source. Even though the infectious agents differ, birds are as susceptible to infectious diseases as humans are. This has been dramatically illustrated in the latest outbreak of the avian H5N1 influenza virus in South East Asia and Europe. Similarly in 2004 in western Canada there was an outbreak caused by influenza strain, H7N3 whereby many birds died and many more were destroyed. Not only do such diseases impact on the chicken industry directly, but they also affect the reliability of this food supply. In my research I study several avian viral diseases with the aim of being able to better understand them, provide diagnostic tools for detecting them and developing vaccines or antiviral strategies to better protect birds from these diseases. In the current proposal and in my more recent research I have focussed on a group of viruses called fowl adenoviruses (FAdVs) which infect mainly chickens. While some infections with FAdVs appear to be asymptomatic, other FAdVs are highly virulent with high death rates and some FAdVs seem to compromise the ability of the immune system to counteract infection with other microbial agents. My research has already uncovered major differences in the genetic composition of avian versus mammalian adenoviruses and I believe these differences in avian adenoviruses relate directly to their specific interaction with the avian host and some are responsible for the biological effects different FAdVs have on the infected birds. In order to determine which genes are responsible for various aspects of virus replication and pathology in the host, I developed a simple (FAdmid) system in which I can either remove a complete gene or alter it. Using this method, I will generate a panel of FAdV mutants defective in various genes unique to FAdV and test the effect of these mutants on virus replication, first in cell culture to determine which genes are essential for virus replication, and then in chickens to monitor differences in pathogenesis and immune response between birds infected with the wild type (unchanged) virus vs the mutated ones.