Innovation Center for Medical Redox Navigation, Kyushu University, Fukuoka, Japan.
Virology. 2011 Apr 25;413(1):12-8. doi: 10.1016/j.virol.2011.02.014. Epub 2011 Mar 6.
Herpes simplex virus entry into cells requires the binding of envelope glycoprotein D (gD) to an entry receptor. Depending on the cell, entry occurs by different mechanisms, including fusion at the cell surface or endocytosis. Here we examined the entry mechanism through a non-HSV receptor mediated by a soluble bi-specific adapter protein composed of recognition elements for gD and the EGF receptor (EGFR). Virus entered into endosomes using either EGF or an EGFR-specific single chain antibody (scFv) for receptor recognition. Infection was less efficient with the EGF adapter which could be attributed to its weaker binding to a viral gD. Infection mediated by the scFv adapter was pH sensitive, indicating that gD-EGFR bridging alone was insufficient for capsid release from endosomes. We also show that the scFv adapter enhanced infection of EGFR-expressing tumor tissue in vivo. Our results indicate that adapters may retarget HSV infection without drastically changing the entry mechanism.
单纯疱疹病毒进入细胞需要包膜糖蛋白 D（gD）与进入受体结合。根据细胞的不同，进入的机制也不同，包括细胞表面融合或内吞作用。在这里，我们通过一种非单纯疱疹病毒受体研究了进入机制，该受体由 gD 和表皮生长因子受体（EGFR）的识别元件组成的可溶性双特异性衔接蛋白组成。病毒通过 EGF 或 EGFR 特异性单链抗体（scFv）进入内体进行受体识别。用 EGF 衔接子进行感染的效率较低，这可能归因于其与病毒 gD 的结合较弱。由 scFv 衔接子介导的感染对 pH 敏感，表明单独的 gD-EGFR 桥接不足以从内体中释放衣壳。我们还表明，scFv 衔接子增强了 EGFR 表达的肿瘤组织在体内的感染。我们的结果表明，衔接子可以重新靶向单纯疱疹病毒感染，而不会大大改变进入机制。
