Role of T cell subsets in Marek’s disease virus pathogenesis

T 细胞亚群在马立克氏病病毒发病机制中的作用

• 批准号: 453660907
• 负责人: Professor Dr. Benedikt Bertold Kaufer, Ph.D.
• 金额: --
• 依托单位: Institut für Virologie (WE05)
• 依托单位国家: 德国
• 项目类别: Research Units
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/453660907?language=en
• 关键词: Role; cell; subsets; Marek; disease

Marek’s disease virus (MDV) is a highly oncogenic alphaherpesvirus that infects chickens and causes paralysis, immunosuppression and deadly lymphomas. MDV-induced lymphomas are considered to be the most prevalent clinically-diagnosed cancer in animals and the virus causes substantial economic losses in poultry industry worldwide. In susceptible chickens, MDV infection can cause mortality of up to 100%, depending on the genetic background of the host and the virulence of the virus strain. Even though current MDV vaccines are highly effective in minimizing commercial losses due to tumor formation, they do not elicit sterilizing immunity, allowing a continued evolution of MDV strains in vaccinated chickens. Since the advent of widespread vaccination, there has been a continuous increase in the virulence of MDV field strains. These more virulent strains are able to overcome vaccine protection and pose a serious threat to poultry production. Therefore, we need a better understanding of MDV pathogenesis and vaccine responses in chickens to develop more potent vaccines that control this deadly pathogen.Despite many years of research, the role of T cell subsets in MDV pathogenesis and vaccine protection remains poorly understood, mostly due to the lack of reverse genetics in chickens. The aim of work package 6 (WP6) is i) to determine the role of γδ T cells in MDV infection, ii) to assess if they are important for vaccine protection and iii) to investigate if MDV pathogenesis is dependent on the presence of αβ T cells. To address these aims, we will use αβ and γδ T cell knockout chickens in combination with molecular and immunological methods. The proposed experiments will not only shed light on the role of these T cell subsets in MDV pathogenesis and vaccine protection but also expand the knowledge on the life cycle of this highly oncogenic virus.The individual research projects within FOR5130 benefit from the collaborations among each other and provide a better insight into the immune system of chickens in relation to important pathogens.

马立克氏病病毒(MDV)是一种高度致癌的甲型疱疹病毒，感染鸡并导致瘫痪、免疫抑制和致命的淋巴瘤。MDV诱导的淋巴瘤被认为是临床上最常见的动物癌症，该病毒在世界范围内给养禽业造成了巨大的经济损失。在敏感的鸡中，MDV感染可导致高达100%的死亡，这取决于宿主的遗传背景和病毒株的毒力。尽管目前的MDV疫苗在最大限度地减少因肿瘤形成而造成的商业损失方面非常有效，但它们不能引起灭菌免疫，使MDV毒株在接种疫苗的鸡中继续进化。自从广泛接种疫苗以来，MDV野毒株的毒力一直在不断增加。这些毒力更强的菌株能够克服疫苗保护，对家禽生产构成严重威胁。因此，我们需要更好地了解MDV在鸡体内的致病机理和疫苗反应，以开发出更有效的疫苗来控制这种致命的病原体。尽管多年来的研究，T细胞亚群在MDV致病和疫苗保护中的作用仍然知之甚少，这主要是由于鸡缺乏反向遗传学。工作包6(WP6)的目的是：1)确定γδT细胞在αβ感染中的作用；2)评估它们对疫苗保护是否重要；3)研究MDV的致病机制是否依赖于MDV T细胞的存在。为了达到这些目的，我们将使用αβ和γδT细胞敲除鸡结合分子和免疫学方法。拟议的实验不仅将阐明这些T细胞亚群在MDV致病机理和疫苗保护中的作用，而且还将扩大对这种高度致癌病毒的生命周期的了解。FOR5130中的各个研究项目受益于彼此之间的合作，并提供了更好的洞察鸡的免疫系统与重要病原体的关系。