A viral protein that selectively downregulates ICAM-1 and B7-2 and modulates T cell costimulation
A viral protein that selectively downregulates ICAM-1 and B7-2 and modulates T cell costimulation
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DOI：
10.1172/jci12432
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发表时间：
2001-06-01
影响因子：
15.9
通讯作者：
Ganem, D
中科院分区：
文献类型：
--
作者：
Coscoy, L;Ganem, D
卡波西肉瘤相关疱疹病毒（KSHV）是一种与艾滋病相关的淋巴组织增生性疾病和KS相关的B淋巴细胞因子。我们和其他人早先已经鉴定了两个病毒基因，K3和K5，它们编码内质网蛋白，通过增强内吞作用下调表面MHC-I链。在这里，我们已经检查了这些蛋白质的能力，影响其他宿主表面蛋白的免疫识别和激活牵连的处置。我们报告说，K5，而不是K3，在BJAB细胞的表达显着降低ICAM-1和B7-2的表面表达; B7-1的表达不受影响。这种K5诱导的减少可以通过共表达发动蛋白的显性负突变体来逆转，这表明ICAM和B7-2表面表达的丧失是由于它们增强的内吞作用。这种下调在功能上是重要的，因为KS转染的B细胞在诱导T细胞活化的能力上显示出实质性的损伤。因此，K5是免疫突触形成和T细胞共刺激的病毒调节剂的第一个例子。我们认为，它的表达减少了T细胞对KSHV感染的B细胞在感染早期的反应，从而减少了抗病毒细胞因子的释放和CTL产生的刺激信号的产生。
Kaposi's sarcoma-associated (KS-associated) herpesvirus (KSHV) is a B-lymphotropic agent linked to AIDS-related lymphoproliferative disorders and KS. We and others have earlier identified two viral genes, K3 and K5, that encode endoplasmic reticulum proteins that downregulate surface MHC-I chains by enhancing their endocytosis. Here we have examined the ability of these proteins to influence the disposition of other host surface proteins implicated in immune recognition and activation. We report that K5, but not K3, expression in BJAB cells dramatically reduces ICAM-1 and B7-2 surface expression; B7-1 expression is unaffected. This K5-induced reduction can be reversed by coexpression of a dominant negative mutant of dynamin, indicating that the loss of ICAM and B7-2 surface expression is due to their enhanced endocytosis. This downregulation is functionally significant, because KS-transfected B cells show substantial impairment in their ability to induce T cell activation. K5 is thus the first example of a viral modulator of immunological synapse formation and T cell costimulation. We propose that its expression reduces T cell responses to KSHV-infected B cells early in infection, thereby diminishing antiviral cytokine release and the production of stimulatory signals for CTL generation.