Glycoprotein D actively induces rapid internalization of two nectin-1 isoforms during herpes simplex virus entry.
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.
Stiles
Katie M
KM
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.
Krummenacher
Claude
C
Department of Biochemistry, School of Dental Medicine University of Pennsylvania, Philadelphia, PA 19104, USA.
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
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