Department of Microbiology, School of Dental Medicine University of Pennsylvania, 240 S. 40th St., Philadelphia, PA 19104, USA.
Department of Biochemistry, School of Dental Medicine University of Pennsylvania, Philadelphia, PA 19104, USA.
Virology. 2010 Mar 30;399(1):109-119. doi: 10.1016/j.virol.2009.12.034. Epub 2010 Jan 20.
Entry of herpes simplex virus (HSV) occurs either by fusion at the plasma membrane or by endocytosis and fusion with an endosome. Binding of glycoprotein D (gD) to a receptor such as nectin-1 is essential in both cases. We show that virion gD triggered the rapid down-regulation of nectin-1 with kinetics similar to those of virus entry. In contrast, nectin-1 was not constitutively recycled from the surface of uninfected cells. Both the nectin-1alpha and beta isoforms were internalized in response to gD despite having different cytoplasmic tails. However, deletion of the nectin-1 cytoplasmic tail slowed down-regulation of nectin-1 and internalization of virions. These data suggest that nectin-1 interaction with a cytoplasmic protein is not required for its down-regulation. Overall, this study shows that gD binding actively induces the rapid internalization of various forms of nectin-1. We suggest that HSV activates a nectin-1 internalization pathway to use for endocytic entry.
单纯疱疹病毒（HSV）的进入要么通过质膜融合，要么通过内吞作用和内体融合。糖蛋白 D（gD）与诸如 nectin-1 的受体的结合在这两种情况下都是必不可少的。我们表明，病毒粒子 gD 触发了 nectin-1 的快速下调，其动力学与病毒进入的动力学相似。相比之下，nectin-1 不是从不感染细胞的表面上连续循环回收的。尽管细胞质尾巴不同，但 gD 触发了 nectin-1alpha 和 nectin-1beta 同种型的内化。然而，nectin-1 细胞质尾巴的缺失减缓了 nectin-1 的下调和病毒粒子的内化。这些数据表明，nectin-1 与细胞质蛋白的相互作用对于其下调不是必需的。总的来说，这项研究表明，gD 结合主动诱导各种形式 nectin-1 的快速内化。我们认为 HSV 激活了 nectin-1 内化途径，用于内吞进入。
