The herpes simplex virus receptor nectin-1 is down-regulated after trans-interaction with glycoprotein D.

Publication Type	Academic Article
Authors	Stiles K, Milne R, Cohen G, Eisenberg R, Krummenacher C
Journal	Virology
Volume	373
Issue	1
Pagination	98-111
Date Published	02/20/2008
ISSN	0042-6822
Keywords	Cell Adhesion Molecules, Down-Regulation, Herpesvirus 1, Human, Receptors, Virus, Viral Envelope Proteins
Abstract	During herpes simplex virus (HSV) entry, membrane fusion occurs either on the cell surface or after virus endocytosis. In both cases, binding of glycoprotein D (gD) to a receptor such as nectin-1 or HVEM is required. In this study, we co-cultured cells expressing gD with nectin-1 expressing cells to investigate the effects of gD on nectin-1 at cell contacts. After overnight co-cultures with gD expressing cells, there was a down-regulation of nectin-1 in B78H1-C10, SY5Y, A431 and HeLa cells, which HSV enters by endocytosis. In contrast, on Vero cells, which HSV enters at the plasma membrane, nectin-1 was not down-regulated. Further analysis of B78H1-derived cells showed that nectin-1 down-regulation corresponds to the ability of gD to bind nectin-1 and is achieved by internalization and low-pH-dependent degradation of nectin-1. Moreover, gD is necessary for virion internalization in B78H1 cells expressing nectin-1. These data suggest that the determinants of gD-mediated internalization of nectin-1 may direct HSV to an endocytic pathway during entry.
PubMed ID	18076965
PubMed Central ID	PMC536050