A highly selective CC chemokine receptor (CCR)8 antagonist encoded by the poxvirus molluscum contagiosum
A highly selective CC chemokine receptor (CCR)8 antagonist encoded by the poxvirus molluscum contagiosum
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DOI：
10.1084/jem.191.1.171
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发表时间：
2000-01-03
影响因子：
15.3
通讯作者：
Schwartz, TW
中科院分区：
文献类型：
--
作者：
Lüttichau, HR;Stine, J;Schwartz, TW
从人传染性软疣痘病毒（MCV）提取的MC148 CC趋化因子与人疱疹病毒8 （HHV8）编码的病毒巨噬细胞炎症蛋白(vip)-II在16个分类的人趋化因子受体中平行进行了探测。在使用放射性标记的内源性趋化因子和放射性标记的MC148的竞争结合中，MC148仅与CCR8具有高亲和力结合。在钙动员试验中，MC148本身对任何趋化因子受体都没有影响。但以剂量依赖的方式阻断内源性I-309趋化因子对CCR8的刺激作用，而不影响趋化因子诱导的任何其他受体的信号传导。相比之下，vMIP-II对16种趋化因子受体中的10种起拮抗剂作用，涵盖所有四类：XCR、CCR、CXCR和CX3CR。在趋化性实验中，MC148特异性地阻断了i -309诱导的反应，但是，例如，不阻断基质细胞衍生因子1 α、单核细胞趋化蛋白1或白细胞介素8诱导的趋化性。因此，我们得出结论，这两种病毒选择两种不同的方式来阻断趋化因子系统：HHV8编码广谱趋化因子拮抗剂vMIP-II，而MCV编码高选择性CCR8拮抗剂MC148，可以想象干扰单核细胞入侵和树突状细胞功能。由于其药理选择性，MC148蛋白可能是描述CCR8及其内源性配体I-309所起作用的有用工具。
The MC148 CC chemokine from the human poxvirus molluscum contagiosum (MCV) was probed in parallel with viral macrophage inflammatory protein (vMIP)-II encoded by human herpesvirus 8 (HHV8) in 16 classified human chemokine receptors. In competition binding using radiolabeled endogenous chemokines as well as radiolabeled MC148, MC148 bound with high affinity only to CCR8. In calcium mobilization assays, MC148 had no effect on its own on any of the chemokine receptors. but in a dose-dependent manner blocked the stimulatory effect of the endogenous I-309 chemokine on CCR8 without affecting chemokine-induced signaling of any other receptor. In contrast, vMIP-II acted as an antagonist on 10 of the 16 chemokine receptors, covering all four classes: XCR, CCR, CXCR, and CX3CR. In chemotaxis assays, MC148 specifically blocked the I-309-induced response but, for example, not stromal cell-derived factor 1 alpha, monocyte chemoattractant protein 1, or interleukin 8-induced chemotaxis. We thus concluded that the two viruses choose two different ways to block the chemokine system: HHV8 encodes the broad-spectrum chemokine antagonist vMIP-II, whereas MCV encodes a highly selective CCR8 antagonist, MC148, conceivably to interfere with monocyte invasion and dendritic cell function. Because of its pharmacological selectivity, the MC148 protein could be a useful tool in the delineation of the role played by CCR8 and its endogenous ligand, I-309.