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）在鸡体内引起一种毁灭性的T细胞肿瘤。细胞表面MHC I类表达的下调是溶解性MDV感染的一个标志。我们的目标是全面了解MHC I类下调在甲型疱疹病毒诱导疾病发病机制中的意义。拟建的研究重点是病毒干扰MHC I类在病毒传递到皮肤游离病毒产生部位、T细胞潜伏感染的建立和肿瘤形成方面的作用。我们的假设是，在裂解复制周期中表达的(a)病毒基因产物(s)持续下调感染细胞表面的MHC I类，促进病毒存活，在动物体内和动物之间传播，并通过允许逃避细胞毒性T淋巴细胞（CTL）的作用建立潜伏感染。这一假设将通过特定的目标进行验证，首先将重点放在进一步证明候选蛋白在体外诱导MHC I类下调。其次，鉴定病毒蛋白的细胞伴侣，确定病毒特异性MHC I类下调的机制。最后，重要的是，病毒诱导的MHC I类抗原呈递与病毒体内复制和发病机制的相关性将被确定。

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.