Paulson E, Tran C, Collins K, Früh K
The R. W. Johnson Pharmaceutical Research Institute, 3210 Merryfield Row, San Diego, California 92121, USA.
Virology. 2001 Sep 30;288(2):369-78. doi: 10.1006/viro.2001.1086.
The carboxy-terminal region of major histocompatibility complex class I (MHC I) molecules is required for the rapid internalization mediated by Kaposi's sarcoma-associated herpesvirus (KSHV) proteins K3 and K5. The cytoplasmic tail of MHC I contains highly conserved serine phosphorylation sites that have been implicated in intracellular trafficking. Indeed, in vivo labeling experiments reveal a lack of MHC I phosphorylation in K5-transfected HeLa cells. Phosphorylation of the MHC I tail was restored upon mutation of the PHD/LAP domain of K5. However, deletion and mutation studies of the MHC I tail show that both K3 and K5 are able to downregulate MHC I lacking the conserved phosphorylation site. This result suggests that inhibition of phosphorylation reflects, but does not cause, MHC I internalization. Interestingly, K3 and K5 differ from each other, as well as from human immunodeficiency virus nef, with respect to the minimal MHC I tail sequences required for MHC downregulation. These data support the notion that K3 and K5 downregulate MHC I molecules by a distinct molecular mechanism that is different from other viral immune evasion molecules.
I类主要组织相容性复合体（MHC I）分子的羧基末端区域是卡波西肉瘤相关疱疹病毒（KSHV）蛋白K3和K5介导快速内化所必需的。MHC I的细胞质尾部含有高度保守的丝氨酸磷酸化位点，这些位点与细胞内运输有关。实际上，体内标记实验显示，在转染K5的HeLa细胞中缺乏MHC I磷酸化。当K5的PHD/LAP结构域发生突变时，MHC I尾部的磷酸化得以恢复。然而，对MHC I尾部的缺失和突变研究表明，K3和K5都能够下调缺乏保守磷酸化位点的MHC I。这一结果表明，磷酸化的抑制反映但不导致MHC I的内化。有趣的是，就下调MHC I所需的最小MHC I尾部序列而言，K3和K5彼此不同，也与人类免疫缺陷病毒nef不同。这些数据支持了这样一种观点，即K3和K5通过一种与其他病毒免疫逃逸分子不同的独特分子机制下调MHC I分子。
