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Specific targeted binding of herpes simplex virus type 1 to hepatocytes via the human hepatitis B virus preS1 peptide

Gene Therapy volume 11, pages 1087–1098 (2004)Cite this article

Abstract

To improve the utility of herpes simplex virus type 1 (HSV-1) vectors for gene therapy, the viral envelope needs to be manipulated to achieve cell-specific gene delivery. In this report, we have engineered an HSV-1 mutant virus, KgBpK− gC−, deleted for the glycoprotein C (gC) and the heparan sulfate-binding domain (pK) of gB, in order to express gC:preS1 and gC:preS1 active peptide (preS1ap) fusion molecules. PreS1, and a 27 amino acid active peptide inside preS1 (preS1ap), are supposed to be the molecules that the human hepatitis B virus (HBV) needs to bind specifically to hepatocytes. Biochemical analysis demonstrated that the gC:preS1ap fusion molecule was expressed and incorporated into the envelope of the recombinant HSV-1 virus KgBpK−gC:preS1ap. Moreover, KgBpK−gC:preS1ap recombinant virus gained a specific binding activity to an hepatoblastoma cell line (HepG2) with a consequent productive infection. In addition, anti-preS1-specific antibodies were shown to neutralize recombinant virus infectivity, and a synthetic preS1ap peptide was able to elute KgBpK−gC:preS1ap virus bound on HpeG2 cells. These data provide further evidence that HSV-1 can productively infect cells through a specific binding to a non-HSV-1 receptor. Furthermore, these data strongly support the hypothesis that the HBV preS1ap molecule is an HBV ligand to hepatocytes.

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Acknowledgements

We thank Joseph Glorioso for critical reading of the paper. This work was supported by the European commission (Quality of Life, QLK2-CT-1999-00055), and grants from Ministero della Sanità – National Program on AIDS (no. 40D.55) and MIUR-FIRB-2001 (RBNE0127YS_002).

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  1. Department of Experimental and Diagnostic Medicine, Section of Microbiology, University of Ferrara, Ferrara, Italy

    Rafaela Argnani, Luca Boccafogli, Peggy C Marconi & Roberto Manservigi

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Argnani, R., Boccafogli, L., Marconi, P. et al. Specific targeted binding of herpes simplex virus type 1 to hepatocytes via the human hepatitis B virus preS1 peptide. Gene Ther 11, 1087–1098 (2004). https://doi.org/10.1038/sj.gt.3302266

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