Modulation of natural killer cells by human cytomegalovirus.
Modulation of natural killer cells by human cytomegalovirus.
复制标题
人巨细胞病毒对自然杀伤细胞的调节。
DOI：
10.1016/j.jcv.2007.10.027
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发表时间：
2008-03
影响因子：
8.8
通讯作者：
Davison, Andrew J.
中科院分区：
文献类型：
--
作者：
Wilkinson, Gavin W. G.;Tomasec, Peter;Stanton, Richard J.;Armstrong, Melanie;Prod'homme, Virginie;Aicheler, Rebecca;McSharry, Brian P.;Rickards, Carole R.;Cochrane, Daniel;Llewellyn-Lacey, Sian;Wang, Eddie C. Y.;Griffin, Cora A.;Davison, Andrew J.
人巨细胞病毒（HCMV）导致终身持续感染，其生存受到免疫系统强烈的持续选择性压力。HCMV存活能力的一个关键方面在于免疫回避。在这种情况下，经历生产性感染的细胞在体外对自然杀伤（NK）细胞介导的细胞溶解表现出显著的抗性。迄今为止，已经鉴定出六种编码蛋白质的基因（UL 16、UL 18、UL 40、UL 83、UL 141和UL 142）和一种编码微小RNA的基因（miR-UL 112）能够抑制NK细胞识别。尽管HCMV感染有效地激活NK细胞活化受体NKG 2D的配体的表达，但至少三种功能（UL 16、UL 142和miR-UL 112）协同作用以抑制这些配体在细胞表面上的呈递。虽然HCMV下调内源性MHC-I的表达，但其编码MHC-I同源物（UL 18），并且还通过UL 40的作用上调细胞HLA-E的表达。正常细胞间连接的破坏暴露了细胞表面NK细胞活化受体的配体，特别是CD 155。HCMV通过编码一种功能（UL 141）克服了这种脆弱性，该功能在感染后起作用以抑制CD 155的细胞表面表达。HCMV系统地逃避（或更恰当地说，调节）NK细胞识别的机制构成了一个不断增长的理解领域，这增强了我们对人类NK细胞功能基本机制的理解。
Human cytomegalovirus (HCMV) causes lifelong, persistent infections and its survival is under intense, continuous selective pressure from the immune system. A key aspect of HCMV’s capacity for survival lies in immune avoidance. In this context, cells undergoing productive infection exhibit remarkable resistance to natural killer (NK) cell-mediated cytolysis in vitro. To date, six genes encoding proteins (UL16, UL18, UL40, UL83, UL141 and UL142) and one encoding a microRNA (miR-UL112) have been identified as capable of suppressing NK cell recognition. Even though HCMV infection efficiently activates expression of ligands for the NK cell activating receptor NKG2D, at least three functions (UL16, UL142 and miR-UL112) act in concert to suppress presentation of these ligands on the cell surface. Although HCMV downregulates expression of endogenous MHC-I, it encodes an MHC-I homologue (UL18) and also upregulates the expression of cellular HLA-E through the action of UL40. The disruption of normal intercellular connections exposes ligands for NK cell activating receptors on the cell surface, notably CD155. HCMV overcomes this vulnerability by encoding a function (UL141) that acts post-translationally to suppress cell surface expression of CD155. The mechanisms by which HCMV systematically evades (or, more properly, modulates) NK cell recognition constitutes an area of growing understanding that is enhancing our appreciation of the basic mechanisms of NK cell function in humans.
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影响因子：
64.8
作者：
Reyburn, HT;Mandelboim, O;Strominger, JL
通讯作者：
Strominger, JL
影响因子：
3.8
作者：
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Hayward, GS
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100.3
作者：
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Trowsdale, John
影响因子：
20.3
作者：
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通讯作者：
López-Botet, M
影响因子：
15.3
作者：
Routes, John M;Ryan, Sharon;Morris, Kristin;Takaki, Rayna;Cerwenka, Adelheid;Lanier, Lewis L
通讯作者：
Lanier, Lewis L