The Kaposi's sarcoma-related herpesvirus (KSHV)-encoded chemokine νMIP-I is a specific agonist for the CC chemokine receptor (CCR)8
The Kaposi's sarcoma-related herpesvirus (KSHV)-encoded chemokine νMIP-I is a specific agonist for the CC chemokine receptor (CCR)8
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DOI：
10.1084/jem.189.12.1993
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发表时间：
1999-06-21
影响因子：
15.3
通讯作者：
Hedrick, JA
中科院分区：
文献类型：
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作者：
Endres, MJ;Garlisi, CG;Hedrick, JA
卡波西肉瘤相关疱疹病毒（KSHV），也称为人类疱疹病毒8，是卡波西肉瘤和某些淋巴瘤的假定致病因子。虽然KSHV编码几种趋化因子同源物（病毒巨噬细胞炎性蛋白[vMIP]-I，-II和-III），只有vMIP-II的功能特征。我们在这里报告，vMIP-1是CC趋化因子受体（CCR）8的特异性激动剂，优先表达在Th 2 T细胞上。用CCR 8转染的Y3细胞响应于VMIP-1产生钙核，并在体外趋化性测定中强烈响应。在竞争结合实验中，vMIP-1与CCR 8的相互作用显示出特异性和高亲和力。与其在CCR 8的激动剂活性相反，vMIP-1不与CCR 5或检查的11种其他受体中的任何一种相互作用。此外，VMIP-I不能抑制CCR 5介导的HIV感染。这些结果表明，KSHV表达vMIP-Ⅰ可能影响宿主免疫应答的Th 1/Th 2平衡。
The Kaposi's sarcoma-related herpesvirus (KSHV), also designated human herpesvirus 8, is the presumed etiolgic agent of Kaposi's sarcoma and certain lymphomas. Although KSHV encodes several chemokine homologues (viral macrophage inflammatory protein [vMIP]-I, -II, and -III), only vMIP-II has been functionally characterized. We report here that vMIP-I is a specific agonist for the CC chemokine receptor (CCR)8 that is preferentially expressed on Th2 T cells. Y3 cells transfected with CCR8 produced a calcium nux in response to VMIP-I and responded vigorously in in vitro chemotaXis assays. In competition binding experiments, the interaction of vMIP-I with CCR8 was shown to be specific and of high affinity. In contrast to its agonist activity at CCR8, vMIP-I did not interact with CCR5 or any of 11 other receptors examined. Furthermore, VMIP-I was unable to inhibit CCR5-mediated HIV infection. These findings suggest that expression of vMIP-I by KSHV may influence the Th1/Th2 balance of the host immune response.