Mechanism of HSV infection through soluble adapter-mediated virus bridging to the EGF receptor

Kenji Nakano, Masatoshi Kobayashi, Kei Ichiro Nakamura, Takeshi Nakanishi, Ryutaro Asano, Izumi Kumagai, Hideaki Tahara, Michihiko Kuwano, Justus B. Cohen, Joseph C. Glorioso

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Herpes simplex virus entry into cells requires the binding of envelope glycoprotein D (gD) to an entry receptor. Depending on the cell, entry occurs by different mechanisms, including fusion at the cell surface or endocytosis. Here we examined the entry mechanism through a non-HSV receptor mediated by a soluble bi-specific adapter protein composed of recognition elements for gD and the EGF receptor (EGFR). Virus entered into endosomes using either EGF or an EGFR-specific single chain antibody (scFv) for receptor recognition. Infection was less efficient with the EGF adapter which could be attributed to its weaker binding to a viral gD. Infection mediated by the scFv adapter was pH sensitive, indicating that gD-EGFR bridging alone was insufficient for capsid release from endosomes. We also show that the scFv adapter enhanced infection of EGFR-expressing tumor tissue in vivo. Our results indicate that adapters may retarget HSV infection without drastically changing the entry mechanism.

Original languageEnglish
Pages (from-to)12-18
Number of pages7
JournalVirology
Volume413
Issue number1
DOIs
Publication statusPublished - 2011 Apr 25

Keywords

  • Bispecific adapter
  • EGF receptor
  • Endocytosis
  • Fusion
  • HSV entry

ASJC Scopus subject areas

  • Virology

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    Nakano, K., Kobayashi, M., Nakamura, K. I., Nakanishi, T., Asano, R., Kumagai, I., Tahara, H., Kuwano, M., Cohen, J. B., & Glorioso, J. C. (2011). Mechanism of HSV infection through soluble adapter-mediated virus bridging to the EGF receptor. Virology, 413(1), 12-18. https://doi.org/10.1016/j.virol.2011.02.014