Kaposi sarcoma-associated herpes virus targets the lymphotactin receptor with both a broad spectrum antagonist vCCL2 and a highly selective and potent agonist vCCL3
Kaposi sarcoma-associated herpes virus targets the lymphotactin receptor with both a broad spectrum antagonist vCCL2 and a highly selective and potent agonist vCCL3
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DOI：
10.1074/jbc.m702001200
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发表时间：
2007-06-15
影响因子：
4.8
通讯作者：
Schwartz, Thue W.
中科院分区：
文献类型：
--
作者：
Luttichau, Hans R.;Johnsen, Anders H.;Schwartz, Thue W.
大的DNA病毒如疱疹病毒和痘病毒编码靶向和利用其宿主的趋化因子系统的蛋白质。这些蛋白质有可能阻断或改变白细胞向病毒感染部位的精心策划的募集。卡波西肉瘤相关疱疹病毒（KSHV）的基因组编码三种趋化因子样蛋白，命名为vCCL1，vCCL2和vCCL3。在这项研究中，vCCL 3与vCCL 1和vCCL 2平行探测了一组18种分类的人趋化因子受体。在钙动员试验中，vCCL 1作为选择性CCR8激动剂，而vCCL 2被发现作为人趋化因子受体（包括趋化因子受体）的广谱趋化因子拮抗剂。相比之下，vCCL3被发现是人趋光因子受体XCR1的高度选择性激动剂。vCCL 3的效能被发现是10倍高于内源性人XCL 1趋化因子方面的磷脂酰肌醇周转和钙动员以及趋化性。实时荧光定量PCR结果显示XCR1在胎盘和中性粒细胞中有高表达。这些数据与KSHV生命周期中vCCL 2和vCCL 3不同表达谱的报道一致，表明病毒通过激动剂和拮抗剂机制特异性地利用趋化因子受体的新颖、复杂的利用，并表明这种（有点被忽视的）趋化因子受体的独特生理重要性。
Large DNA viruses such as herpesvirus and poxvirus encode proteins that target and exploit the chemokine system of their host. These proteins have the potential to block or change the orchestrated recruitment of leukocytes to sites of viral infection. The genome of Kaposi sarcoma-associated herpes virus (KSHV) encodes three chemokine-like proteins named vCCL1, vCCL2, and vCCL3. In this study vCCL3 was probed in parallel with vCCL1 and vCCL2 against a panel of the 18 classified human chemokine receptors. In calcium mobilization assays vCCL1 acted as a selective CCR8 agonist, whereas vCCL2 was found to act as a broad spectrum chemokine antagonist of human chemokine receptors, including the lymphotactin receptor. In contrast vCCL3 was found to be a highly selective agonist for the human lymphotactin receptor XCR1. The potency of vCCL3 was found to be 10-fold higher than the endogenous human XCL1 chemokine in respect to phosphatidylinositol turnover and calcium mobilization as well as chemotaxis. High expression of XCR1 was found in placenta and neutrophils by real-time PCR. These data are consistent with reports of different expression profiles for vCCL2 and vCCL3 during the life cycle of KSHV, indicate a novel, sophisticated exploitation by the virus of specifically the lymphotactin receptor by both agonist and antagonist mechanisms, and suggest a unique physiological importance of this (somewhat overlooked) chemokine receptor.