Biology of fowl adenoviruses

禽类健康，包括保护其不受传染性病原体的侵害，是向世界大部分人口可靠地提供这一主食来源的一个重要组成部分。尽管传染源不同，但鸟类和人类一样容易感染传染病。最近在东南亚和欧洲爆发的H5N1禽流感病毒就充分说明了这一点。同样，2004年在加拿大西部爆发了由H7N3流感毒株引起的疫情，许多鸟类死亡，更多的鸟类被摧毁。这些疾病不仅直接影响养鸡业，而且还影响到这种食品供应的可靠性。在我的研究中，我研究了几种鸟类病毒性疾病，目的是能够更好地了解它们，提供检测它们的诊断工具，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，我把重点放在一组称为禽腺病毒（FAdV）的病毒上，它们主要感染鸡。虽然FAdV的一些感染似乎是无症状的，但其他FAdV具有高毒性和高死亡率，并且一些FAdV似乎损害免疫系统抵抗其他微生物剂感染的能力。我的研究已经发现了鸟类与哺乳动物腺病毒在遗传组成上的主要差异，我相信这些差异与鸟类腺病毒与鸟类宿主的特异性相互作用直接相关，并且一些差异是不同FAdV对受感染鸟类的生物学效应的原因。为了确定哪些基因负责病毒在宿主中复制和病理的各个方面，我开发了一个简单的（FAdmid）系统，在该系统中，我可以去除完整的基因或改变它。使用这种方法，我将产生一组FAdV突变体，这些突变体在FAdV特有的各种基因中有缺陷，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是病毒复制所必需的，然后在鸡中监测感染野生型（未改变）病毒与突变病毒的鸟类之间的发病机制和免疫反应的差异。

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.