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

Katie M. Stiles, Richard S.B. Milne, Gary H. Cohen, Roselyn J. Eisenberg, Claude Krummenacher

Research output: Contribution to journalArticle

40 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)98-111
Number of pages14
JournalVirology
Volume373
Issue number1
DOIs
StatePublished - Mar 30 2008

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Keywords

  • Down-regulation
  • Endocytosis
  • Entry
  • Glycoprotein
  • HSV
  • Herpes simplex virus
  • Nectin-1
  • Receptor

ASJC Scopus subject areas

  • Virology

Cite this

Stiles, K. M., Milne, R. S. B., Cohen, G. H., Eisenberg, R. J., & Krummenacher, C. (2008). The herpes simplex virus receptor nectin-1 is down-regulated after trans-interaction with glycoprotein D. Virology, 373(1), 98-111. https://doi.org/10.1016/j.virol.2007.11.012