Wang Xin, Huong Shu-Mei, Chiu Marie L, Raab-Traub Nancy, Huang Eng-Shang
Lineberger Comprehensive Cancer Center, Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7295, USA.
Nature. 2003 Jul 24;424(6947):456-61. doi: 10.1038/nature01818.
Human cytomegalovirus (HCMV) is a widespread opportunistic herpesvirus that causes severe and fatal diseases in immune-compromised individuals, including organ transplant recipients and individuals with AIDS. It is also a leading cause of virus-associated birth defects and is associated with atherosclerosis and coronary restenosis. HCMV initiates infection and intracellular signalling by binding to its cognate cellular receptors and by activating several signalling pathways including those mediated by mitogen-activated protein kinase, phosphatidylinositol-3-OH kinase, interferons, and G proteins. But a cellular receptor responsible for viral entry and HCMV-induced signalling has yet to be identified. Here we show that HCMV infects cells by interacting with epidermal growth factor receptor (EGFR) and inducing signalling. Transfecting EGFR-negative cells with an EGFR complementary DNA renders non-susceptible cells susceptible to HCMV. Ligand displacement and crosslinking analyses show that HCMV interacts with EGFR through gB, its principal envelope glycoprotein. gB preferentially binds EGFR and EGFR-ErbB3 oligomeric molecules in Chinese hamster ovary cells transfected with erbB family cDNAs. Taken together, these data indicate that EGFR is a necessary component for HCMV-triggered signalling and viral entry.
人巨细胞病毒（HCMV）是一种广泛传播的机会性疱疹病毒，可在免疫功能低下的个体中引发严重和致命疾病，这些个体包括器官移植受者和艾滋病患者。它也是病毒相关出生缺陷的主要原因，还与动脉粥样硬化和冠状动脉再狭窄有关。HCMV通过与其同源细胞受体结合并激活多种信号通路来启动感染和细胞内信号传导，这些信号通路包括由丝裂原活化蛋白激酶、磷脂酰肌醇-3-羟基激酶、干扰素和G蛋白介导的信号通路。但是，负责病毒进入和HCMV诱导信号传导的细胞受体尚未确定。在此我们表明，HCMV通过与表皮生长因子受体（EGFR）相互作用并诱导信号传导来感染细胞。用EGFR互补DNA转染EGFR阴性细胞可使原本不易感的细胞对HCMV易感。配体置换和交联分析表明，HCMV通过其主要包膜糖蛋白gB与EGFR相互作用。在转染了erbB家族cDNA的中国仓鼠卵巢细胞中，gB优先结合EGFR和EGFR-ErbB3寡聚分子。综上所述，这些数据表明EGFR是HCMV触发信号传导和病毒进入所必需的成分。
