title: Herpes simplex virus glycoprotein D relocates nectin-1 from intercellular contacts.
abstract: 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.
authors.affiliation: Department of Biochemistry, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Arjun K
authors.initials: AK
authors.lastname: Bhargava
authors.affiliation: Department of Biological Sciences, College of Science and Mathematics, Rowan University, Glassboro, NJ 08028, USA.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Rothlauf
authors.affiliation: Department of Biological Sciences, College of Science and Mathematics, Rowan University, Glassboro, NJ 08028, USA; Department of Biomedical and Translational Sciences, College of Science and Mathematics, Rowan University, Glassboro, NJ 08028, USA. Electronic address: krummenacher@rowan.edu.
authors.forename: Claude
authors.initials: C
authors.lastname: Krummenacher
mesh_terms: D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D006561:Herpes Simplex / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007365:Intercellular Junctions / Q000235:genetics / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D000075983:Nectins; D011485:Protein Binding; D021381:Protein Transport; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; C000619010:NECTIN1 protein, human; D000075983:Nectins; D014759:Viral Envelope Proteins; C108835:afadin; C039447:glycoprotein D, Human herpesvirus 1
keywords: Cell adhesion; Glycoprotein; Herpes simplex virus; Nectin-1; Receptor; Viral entry