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- Title
Specific targeted binding of herpes simplex virus type 1 to hepatocytes via the human hepatitis B virus preS1 peptide.
- Authors
Argnani, Rafaela; Boccafogli, Luca; Marconi, Peggy C.; Manservigi, Roberto
- 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.Gene Therapy (2004) 11, 1087-1098. doi:10.1038/sj.gt.3302266 Published online 1 April 2004
- Subjects
HEPATITIS B; HEPATITIS B virus; HERPES simplex virus; LIVER cells; GENE therapy; GENETIC engineering
- Publication
Gene Therapy, 2004, Vol 11, Issue 13, p1087
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/sj.gt.3302266