Seidel Einat, Le Vu Thuy Khanh, Bar-On Yotam, Tsukerman Pinchas, Enk Jonatan, Yamin Rachel, Stein Natan, Schmiedel Dominik, Oiknine Djian Esther, Weisblum Yiska, Tirosh Boaz, Stastny Peter, Wolf Dana G, Hengel Hartmut, Mandelboim Ofer
The Lautenberg Center for General and Tumor Immunology, The Faculty of Medicine, The Hebrew University Medical School, IMRIC, Jerusalem 9112001, Israel.
Institute for Virology of the University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany.
Cell Rep. 2015 Feb 17;10(6):968-982. doi: 10.1016/j.celrep.2015.01.029. Epub 2015 Feb 12.
Natural killer (NK) cells mediate innate immune responses against hazardous cells and are particularly important for the control of human cytomegalovirus (HCMV). NKG2D is a key NK activating receptor that recognizes a family of stress-induced ligands, including MICA, MICB, and ULBP1-6. Notably, most of these ligands are targeted by HCMV proteins and a miRNA to prevent the killing of infected cells by NK cells. A particular highly prevalent MICA allele, MICA008, is considered to be an HCMV-resistant "escape variant" that confers advantage to human NK cells in recognizing infected cells. However, here we show that HCMV uses its viral glycoprotein US9 to specifically target MICA008 and thus escapes NKG2D attack. The finding that HCMV evolved a protein dedicated to countering a single host allele illustrates the dynamic co-evolution of host and pathogen.
自然杀伤（NK）细胞介导针对危险细胞的先天性免疫反应，对控制人类巨细胞病毒（HCMV）尤为重要。NKG2D是一种关键的NK激活受体，可识别包括MICA、MICB和ULBP1-6在内的一系列应激诱导配体。值得注意的是，这些配体中的大多数都被HCMV蛋白和一种微小RNA靶向，以防止NK细胞杀死受感染细胞。一种特别高度流行的MICA等位基因MICA008被认为是一种抗HCMV的“逃逸变体”，它赋予人类NK细胞识别受感染细胞的优势。然而，我们在此表明，HCMV利用其病毒糖蛋白US9特异性靶向MICA008，从而逃避NKG2D的攻击。HCMV进化出一种专门对抗单个宿主等位基因的蛋白质这一发现，说明了宿主与病原体之间动态的共同进化。
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