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The synthesis and immunogenicity of varicella-zoster virus glycoprotein E and immediate-early protein (IE62) expressed in recombinant herpes simplex virus-1.

Abstract
In order to evaluate the conditions for optimal expression and immunogenicity of varicella-zoster virus (VZV) proteins in a herpes simplex virus-1 (HSV-1) vector, we selected the VZV glycoprotein E (gE), encoded by ORF 68 and the VZV product of ORF 62, an immediate-early major tegument protein (IE62). Three HSV/VZV recombinants were generated: (1) VZV gE protein coding sequences along with the promoter region were inserted into the thymidine kinase (TK) gene of HSV-1 strain KOS; (2) VZV gE expressed from the HSV-1 ICP4 promoter was inserted into the glycoprotein C (gC) gene of HSV-1 strain F; and (3) VZV IE62 protein coding sequences under the control of the HSV-1 ICP4 promoter were inserted into the gC gene of HSV-1 strain F. Immunoblot analysis and immunoperoxidase staining of infected cell monolayers demonstrated vector expression of VZV proteins. Following intracranial inoculation in mice, both VZV gE-HSV (TK) and VZV IE62-HSV (gC) induced an IgG response against VZV gE or VZV IE62. When tested in cytotoxicity assays using T-lymphocytes from VZV immune human donors, the range of precursor frequencies for T-lymphocytes that recognized VZV gE or VZV IE62 was similar whether these proteins were expressed by HSV-1 or a vaccinia vector. These experiments demonstrate that HSV-1 is a competent vector for expression of these VZV proteins and support the feasibility of engineering a combined vaccine for these closely related alpha-herpesviruses.
AuthorsP W Lowry, C M Koropchak, C Y Choi, E S Mocarski, E R Kern, P R Kinchington, A M Arvin
JournalAntiviral research (Antiviral Res) Vol. 33 Issue 3 Pg. 187-200 (Feb 1997) ISSN: 0166-3542 [Print] Netherlands
PMID9037375 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antigens, Viral
  • Antiviral Agents
  • IE62 protein, Human herpesvirus 3
  • Immediate-Early Proteins
  • Recombinant Fusion Proteins
  • Trans-Activators
  • Viral Envelope Proteins
  • glycoprotein E, varicella-zoster virus
  • Acyclovir
Topics
  • Acyclovir (pharmacology)
  • Animals
  • Antigens, Viral (biosynthesis, genetics, immunology)
  • Antiviral Agents (pharmacology)
  • Blotting, Southern
  • Chlorocebus aethiops
  • Cytotoxicity Tests, Immunologic
  • Genetic Vectors
  • Guinea Pigs
  • Herpes Simplex (immunology, physiopathology, virology)
  • Herpesvirus 1, Human (drug effects, genetics, isolation & purification, pathogenicity)
  • Herpesvirus 3, Human (genetics, immunology)
  • Humans
  • Immediate-Early Proteins (biosynthesis, genetics, immunology)
  • Immunoblotting
  • Mice
  • Mice, Inbred BALB C
  • Recombinant Fusion Proteins (biosynthesis, genetics, immunology)
  • Recombination, Genetic
  • T-Lymphocytes, Cytotoxic (immunology)
  • Trans-Activators (biosynthesis, genetics, immunology)
  • Vero Cells
  • Viral Envelope Proteins (biosynthesis, genetics, immunology)

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