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In vivo complementation studies of a glycoprotein H-deleted herpes simplex virus-based vector
P G Speck1, S Efstathiou, A C Minson
1Department of Pathology, University of Cambridge, UK.
The Journal of General Virology
|October 1, 1996
Summary
Herpes simplex virus (HSV) mutants are crucial for safe gene therapy and vaccines. A new glycoprotein H-negative (gH-) virus system minimizes replication-competent virus, enhancing safety for nervous system gene delivery.
Area of Science:
- Virology
- Gene Therapy
- Neuroscience
Background:
- Herpes simplex virus (HSV) is explored as a gene delivery vector and live vaccine carrier.
- Development requires safe, disabled virus mutants incapable of causing disease.
- Replication-defective vectors pose risks if complemented by wild-type virus.
Purpose of the Study:
- To develop a safe replication-defective HSV vector system.
- To ensure helper cell lines do not generate replication-competent virus.
- To assess the in vivo safety and complementation potential of a gH- HSV mutant.
Main Methods:
- Construction and characterization of a glycoprotein H-negative (gH-) HSV mutant.
- Utilizing a gH- virus/helper cell line combination for virus stock generation.
- In vivo studies in mice to evaluate gH- virus pathogenicity, latency, and complementation with wild-type HSV.
Main Results:
- A gH- virus/helper cell system produced helper-free defective virus stocks with replication-competent virus at a frequency <1 in 10(9) p.f.u.
- gH- virus showed reduced pathogenicity and latency in mice compared to wild-type HSV.
- Complementation by wild-type HSV was observed in a minority of animals, but gH- virus often suppressed wild-type HSV neuroinvasion.
Conclusions:
- The gH- virus/helper cell system provides a safe background for constructing replication-defective gene delivery vectors.
- gH- HSV mutants demonstrate reduced virulence and potential for in vivo safety.
- This system advances the development of safer HSV-based gene therapy and vaccine vectors.