Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Virology. 2010 Sep 30;405(2):457-63. doi: 10.1016/j.virol.2010.06.041. Epub 2010 Jul 15.
Marek's disease is a devastating neoplastic disease of chickens caused by Marek's disease virus (MDV). MDV down-regulates surface expression of MHC class I molecules, although the mechanism has remained elusive. MDV harbors a UL49.5 homolog that has been shown to down-regulate MHC class I expression in other Varicelloviruses. Using in vitro assays, we showed that MDV pUL49.5 down-regulates MHC class I directly and identified its cytoplasmic tail as essential for this function. In vivo, viruses lacking the cytoplasmic tail of pUL49.5 showed no differences in MD pathogenesis compared to revertant viruses in highly susceptible chickens of the B(19)B(19) MHC class I haplotype, while there was a mild reduction in pathogenic potential of the deletion viruses in chickens more resistant to MD pathogenesis (MHC:B(21)B(21)). We concluded that the pathogenic effect of MHC class I down-regulation mediated by pUL49.5 is small because virus immune evasion possibly requires more than one viral protein.
马立克氏病是一种毁灭性的鸡肿瘤性疾病，由马立克氏病病毒（MDV）引起。MDV 下调 MHC I 类分子的表面表达，尽管其机制仍不清楚。MDV 携带一个 UL49.5 同源物，该同源物已被证明可下调其他疱疹病毒中的 MHC I 类表达。通过体外实验，我们表明 MDV pUL49.5 直接下调 MHC I 类，并确定其细胞质尾巴对该功能至关重要。在体内，缺乏 pUL49.5 细胞质尾巴的病毒在高度易感的 B(19)B(19)MHC I 单倍型鸡中与回复病毒在 MD 发病机制方面没有差异，而在对 MD 发病机制更具抵抗力的鸡中，缺失病毒的致病潜力略有降低（MHC：B(21)B(21)）。我们得出结论，pUL49.5 介导的 MHC I 类下调的致病效应很小，因为病毒免疫逃避可能需要不止一种病毒蛋白。
