HSV-1 virions engineered for specific binding to cell surface receptors

Paola Grandi, Samuel Wang, Deborah Schuback, Victor Krasnykh, Matthew Spear, David T. Curiel, Roberto Manservigi, Xandra O. Breakefield

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Expression of specific peptide epitopes on the surface of virions has significant potential for studying viral biology and designing vectors for targeted gene therapy. In this study, an HSV-1 amplicon plasmid expressing a modified glycoprotein C (gC), in which the heparan sulfate binding domain was replaced with a His-tag, was used in generating HSV-1 virions. Western blot analysis demonstrated the presence of modified gC in the purified virions. The amplicon vectors were packaged using a gC-, lacZ+ helper virus to generate a mixture of high-titer helper virus (lacZ+) and amplicon vectors (GFP+), which expressed modified gC in the virion envelope. His-tagged virions bound to 293 6H cells expressing a cell surface pseudo-His-tag receptor four-fold more efficiently than to parental 293 cells and also proved more effective than wild-type virus in binding to both cell types. Binding resulted in productive infection by the modified virions with expression of reporter genes and cytopathic effect comparable to those of wild-type virions. Thus, not only can HSV-1 tropism be manipulated to recognize a non-herpes simplex binding receptor, but it is also possible to increase the infective capacity of the vectors beyond that of the wild-type virus via specific ligand receptor combinations.

Original languageEnglish
Pages (from-to)419-427
Number of pages9
JournalMolecular Therapy
Volume9
Issue number3
DOIs
StatePublished - Mar 2004
Externally publishedYes

Keywords

  • Gene therapy
  • HSV receptors
  • HSV-1 glycoproteins
  • Heparan sulfate
  • Targeting
  • Virion envelope
  • Virus entry

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    Grandi, P., Wang, S., Schuback, D., Krasnykh, V., Spear, M., Curiel, D. T., Manservigi, R., & Breakefield, X. O. (2004). HSV-1 virions engineered for specific binding to cell surface receptors. Molecular Therapy, 9(3), 419-427. https://doi.org/10.1016/j.ymthe.2003.12.010