病毒有很多诡计用于躲避免疫系统。在2009年9月7日的Journal of Cell Biology杂志上，Stagg等人揭示了其中的一个病毒诡计的关键细节。该病毒会识别一种蛋白，而这种蛋白使得巨细胞病毒能够关闭机体对其的防御。
巨细胞病毒（Cytomegalovirus）能够通过靶向定位MHC I蛋白躲避免疫系统的监视。当机体受到感染时，MHC I会捕获少量的病毒蛋白，并将其呈现到病毒素T细胞，从而杀死细胞停住继续感染。然而两个巨细胞病毒基因会欺骗细胞泛激素化MHC I 并在蛋白酶体中将其摧毁。为了引起MHC I泛激素化，基因会选择一个叫E3连接酶的蛋白。研究人员解释说，目前，还不是很清楚这个蛋白的身份。
使用RNA干扰技术，Stagg筛选了373种候选物，发现一种叫TRC8的连接酶可以保护MHC I。TRC8的突变体能够截断泛激素化使得MHC I恢复功能。（生物谷Bioon.com）
生物谷推荐原始出处：
The Journal of Cell Biology doi:10.1083/jcb.200906110
The TRC8 E3 ligase ubiquitinates MHC class I molecules before dislocation from the ER
Helen R. Stagg1, Mair Thomas1, Dick van den Boomen1, Emmanuel J.H.J. Wiertz2, Harry A. Drabkin3, Robert M. Gemmill3, and Paul J. Lehner1
1 Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, England, UK
2 University Medical Centre Utrecht, 3584 CX Utrecht, Netherlands
3 Division of Hematology/Oncology, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425
The US2 and US11 gene products of human cytomegalovirus promote viral evasion by hijacking the endoplasmic reticulum (ER)–associated degradation (ERAD) pathway. US2 and US11 initiate dislocation of newly translocated major histocompatibility complex class I (MHC I) from the ER to the cytosol for proteasome-mediated degradation, thereby decreasing cell surface MHC I. Despite being instrumental in elucidating the mammalian ERAD pathway, the responsible E3 ligase or ligases remain unknown. Using a functional small interfering RNA library screen, we now identify TRC8 (translocation in renal carcinoma, chromosome 8 gene), an ER-resident E3 ligase previously implicated as a hereditary kidney cancer gene, as required for US2-mediated MHC I ubiquitination. Depletion of TRC8 prevents MHC I ubiquitination and dislocation by US2 and restores cell surface MHC I. TRC8 forms an integral part of a novel multiprotein ER complex that contains MHC I, US2, and signal peptide peptidase. Our data show that the TRC8 E3 ligase is required for MHC I dislocation from the ER and identify a new complex associated with mammalian ERAD.
