Department of Biology, University of San Francisco, 2130 Fulton Street, San Francisco, CA 94117, USA.
Virus Res. 2013 Sep;176(1-2):312-20. doi: 10.1016/j.virusres.2013.07.002. Epub 2013 Jul 11.
Human cytomegalovirus (HCMV) is a prevalent pathogen worldwide. Although generally harmless in healthy individuals, HCMV can pose a serious threat to immune compromised individuals and developing fetuses in utero. HCMV encodes four genes predicted to give rise to G protein-coupled receptors (GPCRs): US27, US28, UL33, and UL78. The US28 gene product is a functional chemokine receptor that enhances cell growth in some cell types but induces apoptosis in others. In contrast, the US27 gene product has not been demonstrated to signal either constitutively or in a ligand-induced manner. In this study, US27 was expressed in transfected cells, and both cell proliferation and DNA synthesis were significantly increased compared to control cells. PCR array analysis revealed that expression of US27 led to changes in a limited number of cellular genes, but genes that were up-regulated included the pro-survival factor Bcl-x, AP-1 transcription factor components jun and fos, and the IL-6 family cytokine oncostatin M. These results demonstrate that US27 can impact host cell physiology and may shed light on the function of this orphan viral GPCR.
人巨细胞病毒(HCMV)是一种在全球范围内流行的病原体。尽管在健康个体中通常无害,但 HCMV 可能对免疫受损个体和宫内发育中的胎儿构成严重威胁。HCMV 编码四个被预测能产生 G 蛋白偶联受体(GPCR)的基因:US27、US28、UL33 和 UL78。US28 基因产物是一种功能性趋化因子受体,它能增强某些细胞类型的细胞生长,但诱导其他细胞凋亡。相比之下,US27 基因产物尚未被证明以组成型或配体诱导的方式发出信号。在这项研究中,US27 在转染细胞中表达,与对照细胞相比,细胞增殖和 DNA 合成均显著增加。PCR 阵列分析显示,US27 的表达导致少数细胞基因发生变化,但上调的基因包括生存因子 Bcl-x、AP-1 转录因子成分 jun 和 fos 以及 IL-6 家族细胞因子 oncostatin M。这些结果表明,US27 可以影响宿主细胞的生理学,可能揭示这个孤儿病毒 GPCR 的功能。