Immunology of Marek's disease virus infection in chickens

动物传染病对人类和动物的健康具有重要意义。此外，这些疾病给食用畜牧业造成了巨大的经济损失。马立克氏病(MD)是由病毒、马立克氏病病毒或MDV引起的一种鸡的疾病，以淋巴瘤或免疫系统细胞癌的形成为特征。这种疾病为研究免疫系统和控制免疫介质的基因在赋予疾病抵抗力方面的作用提供了一个独特的模型。对MD的耐药性是由基因控制的，已有几个基因被证明在免疫中发挥作用。此外，这可能是第一种商业疫苗面世的癌症。然而，人们对疫苗预防疾病的机制知之甚少。此外，疫苗在消除或减少受感染禽类的病毒脱落方面也不有效。病毒的脱落使其他禽类容易受到感染，更重要的是，为病毒创造了增强其致病能力的机会。该计划旨在从分子和细胞水平研究鸡对MDV感染的免疫反应的诱导和调节。免疫系统的细胞，如T细胞，已被证明在抵御病毒攻击方面具有重要作用。该计划的目标是：1-识别T细胞识别的MDV分子决定因素，从而预防疾病；2-检查羽毛和肺中T细胞对病毒的反应，这是MDV生命周期的关键组织；3-了解羽毛中发生的导致T细胞无法清除羽毛中病毒的事件。预计拟议研究的结果将扩大我们对宿主-病原体相互作用的理解，并为未来旨在设计合理的MD疫苗的研究奠定基础，这种疫苗在控制病毒脱落方面更有效。

Animal infectious diseases are of great importance to human and animal health. Moreover, these diseases impose significant economic losses to the food animal industry. Marek's disease (MD) is a disease of chickens caused by a virus, Marek's disease virus or MDV, and marked by formation of lymphomas, or cancer of immune system cells. This disease provides a unique model for studying the role of immune system and the genes, which control the immune mediators, in conferring resistance to disease. Resistance to MD is genetically controlled and several genes have been shown to play a role in immunity. Moreover, this is probably the first cancer against which a commercial vaccine became available. However, little is known about the mechanisms through which vaccines can prevent disease. Also, the vaccine is not effective at eliminating or reducing virus shedding from the infected birds. Virus shedding predisposes other birds to infection and, more importantly, creates an opportunity for the virus to enhance its disease-causing capacity. The proposed program is intended to investigate, at the molecular and cellular levels, induction and regulation of chicken immune response against MDV infection. Cells of the immune system, such as T cells, have been shown to be important in protection against viral insults. The objectives of this program are to: 1- identify the molecular determinants of MDV recognized by T cells leading to protection against disease, 2- examine T cell responses to the virus in feathers and lungs, which are critical tissues for MDV life cycle, 3- understand the events that occur in feathers rendering T cells unable to eliminate the virus in feathers. It is expected that findings of the proposed studies will expand our understanding of host-pathogen interactions and will also layout the foundation for future studies aimed at designing rational vaccines against MD, which are more effective at control of virus shedding.