Down regulation of MHC class I cell surface expression in Marek's disease virus (MDV) infection and its relevance in vivo

马立克氏病病毒 (MDV) 感染中 MHC I 类细胞表面表达的下调及其体内相关性

• 批准号: 57095562
• 负责人: Professor Dr. Nikolaus Osterrieder
• 金额: --
• 依托单位: Institut für Virologie (WE05)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/57095562?language=en
• 关键词: Down; regulation; MHC; class; cell

Marek's disease virus (MDV) causes a devastating T cell tumor in the chicken. Down regulation of cell surface MHC class I expression is a hallmark of lytic MDV infection. Our goal is to gain a complete understanding of the significance of MHC class I down regulation in the pathogenesis of alphaherpesvirus-induced disease. The proposed studies focus on the role of virus interference with MHC class I with regard to virus delivery to the site of free virus production in the skin, the establishment of latent infection in T celts, and tumor formation. Our hypothesis is that sustained down regulation of MHC class I on the surface of infected cells by (a) viral gene product(s) expressed during the lytic replication cycle facilitates virus survival, spread within and between animals, and the establishment of latent infection by allowing an escape from the action of cytotoxic T lymphocytes (CTL). The hypothesis is tested by specific aims that will first focus on further proof of MHC class I down regulation in vitro induced by candidate proteins. Secondly, cellular partners of the viral proteins will be identified and mechanism(s) of virus-specific MHC class I down regulation determined. Finally and importantly, the relevance of the virus-induced block in MHC class I antigen presentation on virus replication in vivo and pathogenesis will be determined.

马立克氏病病毒（MDV）在鸡体内引起毁灭性的T细胞肿瘤。细胞表面MHC I类表达的下调是裂解性MDV感染的标志。我们的目标是获得一个完整的理解的意义，MHC I类下调的发病机制中的α疱疹病毒引起的疾病。拟议的研究集中在病毒干扰MHC I类的作用，关于病毒递送到皮肤中的游离病毒产生部位，T细胞中潜伏感染的建立和肿瘤形成。我们的假设是，在裂解性复制周期中表达的病毒基因产物对感染细胞表面的I类MHC的持续下调促进了病毒的存活、在动物内和动物之间的传播，以及通过允许逃避细胞毒性T淋巴细胞（CTL）的作用而建立潜伏感染。该假设是测试的具体目标，将首先集中在进一步证明的MHC I类下调在体外诱导的候选蛋白。其次，将鉴定病毒蛋白的细胞伴侣，并确定病毒特异性MHC I类下调的机制。最后，重要的是，将确定病毒诱导的阻断MHC I类抗原呈递对体内病毒复制和发病机制的相关性。