Intracellular Sequestration of the NKG2D Ligand ULBP3 by Human Cytomegalovirus
Intracellular Sequestration of the NKG2D Ligand ULBP3 by Human Cytomegalovirus
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DOI：
10.4049/jimmunol.1000789
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发表时间：
2010-07-15
影响因子：
4.4
通讯作者：
Wills, Mark R.
中科院分区：
文献类型：
--
作者：
Bennett, Neil J.;Ashiru, Omodele;Wills, Mark R.
人CMV（HCMV）编码控制NK细胞活化和细胞毒性的多个基因。这些HCMV编码的基因产物中的一些作为在细胞表面表达的配体调节NK细胞活性，所述配体接合抑制性NK细胞受体，而其他基因产物防止感染的细胞上调结合活化NK细胞受体的配体。一种主要的活化NKR是同型二聚体NKG 2D受体，其在人体内具有八种不同的天然配体。结果表明，HCMV能够阻止这些配体中的五种（MIC A/B和ULBP 1、2和6）的表面表达。在这篇文章中，我们表明，HCMV基因产物UL 142可以防止感染过程中ULBP 3的细胞表面表达。我们进一步表明，UL 142与ULBP 3相互作用，并介导其细胞内滞留在一个区室，共定位与标记的顺式高尔基复合体。在这样做时，UL 142阻止ULBP 3运输到表面并保护转染的细胞免受NK介导的细胞毒性。这是第一次描述能够介导ULBP 3下调的病毒基因。免疫学杂志，2010，185：1093-1102。
Human CMV (HCMV) encodes multiple genes that control NK cell activation and cytotoxicity. Some of these HCMV-encoded gene products modulate NK cell activity as ligands expressed at the cell surface that engage inhibitory NK cell receptors, whereas others prevent the infected cell from upregulating ligands that bind to activating NK cell receptors. A major activating NKR is the homodimeric NKG2D receptor, which has eight distinct natural ligands in humans. It was shown that HCMV is able to prevent the surface expression of five of these ligands (MIC A/B and ULBP1, 2, and 6). In this article, we show that the HCMV gene product UL142 can prevent cell surface expression of ULBP3 during infection. We further show that UL142 interacts with ULBP3 and mediates its intracellular retention in a compartment that colocalizes with markers of the cis-Golgi complex. In doing so, UL142 prevents ULBP3 trafficking to the surface and protects transfected cells from NK-mediated cytotoxicity. This is the first description of a viral gene able to mediate downregulation of ULBP3. The Journal of Immunology, 2010, 185: 1093-1102.