Bhargava Arjun K, Rothlauf Paul W, Krummenacher Claude
Department of Biochemistry, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Biological Sciences, College of Science and Mathematics, Rowan University, Glassboro, NJ 08028, USA.
Virology. 2016 Dec;499:267-277. doi: 10.1016/j.virol.2016.09.019. Epub 2016 Oct 7.
Herpes simplex virus (HSV) uses the cell adhesion molecule nectin-1 as a receptor to enter neurons and epithelial cells. The viral glycoprotein D (gD) is used as a non-canonical ligand for nectin-1. The gD binding site on nectin-1 overlaps with a functional adhesive site involved in nectin-nectin homophilic trans-interaction. Consequently, when nectin-1 is engaged with a cellular ligand at cell junctions, the gD binding site is occupied. Here we report that HSV gD is able to disrupt intercellular homophilic trans-interaction of nectin-1 and induce a rapid redistribution of nectin-1 from cell junctions. This movement does not require the receptor's interaction with the actin-binding adaptor afadin. Interaction of nectin-1 with afadin is also dispensable for virion surfing along nectin-1-rich filopodia. Cells seeded on gD-coated surfaces also fail to accumulate nectin-1 at cell contact. These data indicate that HSV gD affects nectin-1 locally through direct interaction and more globally through signaling.
单纯疱疹病毒（HSV）利用细胞黏附分子nectin-1作为受体进入神经元和上皮细胞。病毒糖蛋白D（gD）作为nectin-1的非典型配体。nectin-1上的gD结合位点与参与nectin-nectin同源性反式相互作用的功能性黏附位点重叠。因此，当nectin-1在细胞连接处与细胞配体结合时，gD结合位点被占据。在此我们报告，HSV gD能够破坏nectin-1的细胞间同源性反式相互作用，并诱导nectin-1从细胞连接处快速重新分布。这种移动不需要受体与肌动蛋白结合衔接蛋白afadin相互作用。nectin-1与afadin的相互作用对于病毒粒子沿着富含nectin-1的丝状伪足冲浪也是可有可无的。接种在gD包被表面的细胞在细胞接触时也无法积累nectin-1。这些数据表明，HSV gD通过直接相互作用在局部影响nectin-1，并通过信号传导在更广泛的范围内产生影响。
