Herpes simplex virus targeting to the EGF receptor by a gD-Specific soluble bridging molecule

Kenji Nakano, Ryutaro Asano, Kouhei Tsumoto, Heechung Kwon, William F. Goins, Izumi Kumagai, Justus B. Cohen, Joseph C. Glorioso

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)

Abstract

Herpes simplex virus 1 (HSV-1) enters cells via initial binding of envelope glycoproteins (g) C and B to cell-surface glycosaminoglycans (GAGs) and subsequent membrane fusion involving envelope gD, gB, and gH/gL. Current insights suggest that the fusion process is initiated by interaction of gD with a cognate cellular receptor, such as the widely distributed cell adhesion molecule nectin-1. To redirect the tropism of HSV-1, we have generated a soluble adapter protein (P-V528LH) comprising the gD-binding variable domain of nectin-1 fused to a single-chain antibody (528LH) recognizing the EGF receptor. The adapter molecule enabled HSV-1 entry into naturally nonpermissive CHO cells expressing the human EGF receptor, but not into CHO cells lacking the receptor, and entry was not observed when the antibody portion of the adapter was replaced with an antibody of different specificity. Adapter-mediated entry increased with the viral dose and was nearly as efficient as direct viral entry into nectin-1-bearing CHO cells. Entry depended on viral gD and was diminished in the absence of cellular GAGs. These experiments represent the first demonstration that a soluble molecule can direct HSV infection via a new receptor, supporting the possible utility of this approach for HSV retargeting.

Original languageEnglish
Pages (from-to)617-626
Number of pages10
JournalMolecular Therapy
Volume11
Issue number4
DOIs
Publication statusPublished - 2005 Apr

Keywords

  • Bispecific bridging molecule
  • Gene therapy
  • Glycoprotein D
  • Herpesvirus
  • Nectin-1
  • Targeting

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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