The herpes simplex virus receptor nectin-1 is down-regulated after trans-interaction with glycoprotein D.
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.
Stiles
Katie M
KM
Department of Microbiology, School of Dental Medicine University of Pennsylvania, Philadelphia, PA 19104, USA.
Milne
Richard S B
RS
Cohen
Gary H
GH
Eisenberg
Roselyn J
RJ
Krummenacher
Claude
C
D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002522:Chlorocebus aethiops; D015536:Down-Regulation; D004705:Endocytosis; D006367:HeLa Cells; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D051379:Mice; D000075983:Nectins; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*
D015815:Cell Adhesion Molecules; C000619010:NECTIN1 protein, human; C000619015:Nectin1 protein, mouse; D000075983:Nectins; D011991:Receptors, Virus; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1