Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Virology. 2010 Feb 20;397(2):369-78. doi: 10.1016/j.virol.2009.11.024. Epub 2009 Dec 9.
Human herpesvirus 8 (HHV-8) is associated with Kaposi's sarcoma (KS), an endothelial cell lesion believed to be initiated and driven primarily by cytokine dysregulation. Among the viral proteins suspected as contributing to viral pathogenesis is the lytically expressed viral G protein-coupled receptor (vGPCR), which can induce various cellular cytokines. CC ligand-2 (CCL2/MCP-1) is a vGPCR-regulated angiogenic chemokine found at elevated levels in KS lesions and induced by HHV-8 infection of endothelial cells. Here we show that vGPCR induces CCL2 in endothelial cells via activation of C/EBPbeta and that vGPCR and C/EBPbeta are critical components of CCL2 induction by HHV-8 infection of endothelial cultures. To our knowledge, this is the first report of vGPCR-mediated cytokine induction, and its characterization, in the context of virus infection. Our results identify a mechanism by which vGPCR can contribute, in a host cell shutoff-independent manner, to viral pathogenesis.
人类疱疹病毒 8 型（HHV-8）与卡波济肉瘤（KS）有关，卡波济肉瘤被认为主要是由细胞因子失调引发和驱动的内皮细胞病变。在被怀疑有助于病毒发病机制的病毒蛋白中，有一种溶解释放的病毒 G 蛋白偶联受体（vGPCR），它可以诱导各种细胞因子。CC 配体-2（CCL2/MCP-1）是一种 vGPCR 调节的血管生成趋化因子，在 KS 病变中水平升高，并被 HHV-8 感染内皮细胞诱导。在这里，我们表明 vGPCR 通过激活 C/EBPbeta 在血管内皮细胞中诱导 CCL2，并且 vGPCR 和 C/EBPbeta 是 HHV-8 感染内皮细胞诱导 CCL2 的关键组成部分。据我们所知，这是在病毒感染背景下首次报道 vGPCR 介导的细胞因子诱导及其特征。我们的研究结果确定了 vGPCR 可以以宿主细胞关闭非依赖性的方式促进病毒发病机制的机制。
