title: Glycoprotein D actively induces rapid internalization of two nectin-1 isoforms during herpes simplex virus entry.
abstract: 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.
authors.affiliation: Department of Microbiology, School of Dental Medicine University of Pennsylvania, 240 S. 40th St., Philadelphia, PA 19104, USA. Electronic address: stileskm@mail.med.upenn.edu.
authors.forename: Katie M
authors.initials: KM
authors.lastname: Stiles
authors.affiliation: Department of Biochemistry, School of Dental Medicine University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Claude
authors.initials: C
authors.lastname: Krummenacher
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002460:Cell Line; D015536:Down-Regulation; D004705:Endocytosis / Q000502:physiology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D006561:Herpes Simplex / Q000821:virology; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006801:Humans; D051379:Mice; D000075983:Nectins; D020033:Protein Isoforms / Q000502:physiology; D014759:Viral Envelope Proteins / Q000502:physiology*; D053586:Virus Internalization
chemical_list: D015815:Cell Adhesion Molecules; C000619010:NECTIN1 protein, human; C000619015:Nectin1 protein, mouse; D000075983:Nectins; D020033:Protein Isoforms; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1