The US27 gene product of human cytomegalovirus enhances signaling of host chemokine receptor CXCR4
The US27 gene product of human cytomegalovirus enhances signaling of host chemokine receptor CXCR4
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DOI：
10.1016/j.virol.2013.02.006
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发表时间：
2013-05-10
期刊：
影响因子：
3.7
通讯作者：
Spencer, Juliet V.
中科院分区：
文献类型：
--
作者：
Arnolds, Kathleen L.;Lares, Angela P.;Spencer, Juliet V.
人巨细胞病毒（HCMV）是疱疹病毒科的成员，其部分地通过模拟细胞因子、趋化因子和趋化因子受体来操纵宿主免疫应答并建立终身潜伏感染。HCMV US 27基因产物是一种假定的趋化因子受体，没有已知的配体。我们产生了稳定的US 27细胞系来筛选趋化因子配体，但意外地发现US 27增强了内源性人类趋化因子受体CXCR 4的活性。与对照相比，表达US 27和CXCR 4的细胞对CXCL 12/SDF-1 α的反应表现出更大的钙动员和增强的趋化性。定量RT-PCR显示，当存在US 27时，CXCR 4表达显著增加，并且通过流式细胞术、蛋白质印迹和免疫荧光显微镜检测到CXCR 4受体水平升高。通过US 27增强CXCR 4信号传导可能代表一种新的策略，通过该策略，HCMV将病毒感染的细胞靶向骨髓，以扩大潜伏感染细胞的储存库。(C)2013 Elsevier Inc. All rights reserved.
Human cytomegalovirus (HCMV) is a member of the Herpesviridae family that manipulates host immune responses and establishes life-long latent infection, in part through mimicry of cytokines, chemokines, and chemokine receptors. The HCMV US27 gene product is a putative chemokine receptor with no known ligands. We generated a stable US27 cell line to screen for chemokine ligands but unexpectedly found that US27 potentiated the activity of an endogenous human chemokine receptor, CXCR4. Cells expressing both US27 and CXCR4 exhibited greater calcium mobilization and enhanced chemotaxis in response to CXCL12/SDF-1 alpha than controls. Quantitative RT-PCR revealed a significant increase in CXCR4 expression when US27 was present, and elevated CXCR4 receptor levels were detected via flow cytometry, western blot, and immunofluorescence microscopy. Potentiation of CXCR4 signaling by US27 could represent a novel strategy by which HCMV targets virus-infected cells to the bone marrow in order to expand the reservoir of latently infected cells. (C) 2013 Elsevier Inc. All rights reserved.