Intracellular signaling by the chemokine receptor US28 during human cytomegalovirus infection
Intracellular signaling by the chemokine receptor US28 during human cytomegalovirus infection
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DOI：
10.1128/jvi.72.7.5535-5544.1998
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发表时间：
1998-07-01
影响因子：
5.4
通讯作者：
Worthen, GS
中科院分区：
文献类型：
--
作者：
Billstrom, MA;Johnson, GL;Worthen, GS
在细胞介导的免疫反应受损的患者中（如肺移植受者和艾滋病患者），巨细胞病毒（CMV）感染可引起严重疾病，如肺炎。然而，尽管宿主的免疫能力可以防止巨细胞病毒疾病，但病毒通过逃避宿主的免疫防御而持续存在。CMV感染内皮的模型已经建立，其中炎症刺激，如CC趋化因子RANTES，结合到内皮细胞表面，在CMV感染后期刺激钙通量。在感染后96小时，cmv感染的细胞表达cmv编码的CC趋化因子受体US28的mRNA，但不表达其他结合RANTES的CC趋化因子受体（CCR1, CCR4, CCR5）的mRNA。受体CMV US28在人肾上皮细胞（293细胞）中的克隆和稳定表达（16）表明，CMV US28与G α (i)和G α(16)蛋白结合，在趋化因子RANTES和MCP-3的作用下激活钙流。此外，共表达US28和G α(16)的细胞通过激活细胞外信号调节激酶对RANTES刺激做出反应，这可能部分归因于特异性G α(16)偶联。因此，通过表达CC趋化因子受体US28， CMV可能利用感染细胞的常驻G蛋白来操纵趋化因子刺激的细胞反应。
In patients with impaired cell-mediated immune responses (e.g., lung transplant recipients and AIDS patients), cytomegalovirus (CMV) infection causes severe disease such as pneumonitis. However, although immunocompetency in the host can protect from CMV disease, the virus persists by evading the host immune defenses. A model of CMV infection of the endothelium has been developed in which inflammatory stimuli, such as the CC chemokine RANTES, bind to the endothelial cell surface, stimulating calcium flux during late times of CMV infection. At 96 h postinfection, CMV-infected cells express mRNA of the CMV-encoded CC chemokine receptor US28 but do not express mRNA of other CC chemokine receptors that bind RANTES (CCR1, CCR4, CCR5). Cloning and stable expression of the receptor CMV US28 in human kidney epithelial cells (293 cells) with and without the heterotrimeric G protein alpha(16) indicated that CMV US28 couples to both G alpha(i) and G alpha(16) proteins to activate calcium flux in response to the chemokines RANTES and MCP-3. Furthermore, cells that coexpress US28 and G alpha(16) responded to RANTES stimulation with activation of extracellular signal-regulated kinase, which could be attributed, in part, to specific G alpha(16) coupling. Thus, through expression of the CC chemokine receptor US28, CMV may utilize resident G proteins of the infected cell to manipulate cellular responses stimulated by chemokines.