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Deletion of the Herpes simplex 1 internal repeat sequences affects pathogenicity in the mouse
F J Jenkins1, A M Donoghue, J R Martin
1Department of Pathology and Infectious Diseases and Microbiology, University of Pittsburgh, and Division of Behavioral Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA. jenkins@pcicirs.pci.pitt.edu
Frontiers in Bioscience : a Journal and Virtual Library
|October 4, 1996
Summary
New herpes simplex virus 1 (HSV-1) recombinants show reduced virulence and neuroinvasion in mice. These modified HSV-1 strains offer a unique model for studying viral pathogenesis and developing safer antiviral strategies.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Herpes simplex virus 1 (HSV-1) is a significant human pathogen.
- Understanding HSV-1 genome structure and its impact on pathogenesis is crucial for developing effective therapies.
- Recombinant viral technologies allow for precise genetic modifications to study viral behavior.
Purpose of the Study:
- To create and characterize novel HSV-1 recombinant viruses with specific genomic alterations.
- To evaluate the in vitro and in vivo properties of these recombinant HSV-1 strains.
- To investigate the potential of these modified viruses as models for studying HSV-1 pathogenesis.
Main Methods:
- Isolation and characterization of three HSV-1 recombinant viruses with defined genome arrangements (P, IS, ILS).
- Deletion of viral DNA sequences and insertion of a mini-Mu genome containing a thymidine kinase gene.
- Growth curve analyses in cell culture and pathogenicity studies in a mouse model (intracerebral and corneal inoculation).
Main Results:
- Recombinant viruses exhibited slightly slower growth in cell culture but similar plaque morphology to wild-type HSV-1.
- Mice infected with recombinant viruses showed significantly increased LD50 values, indicating reduced virulence.
- Recombinant viruses were not neuroinvasive, failed to spread from the cornea to sensory ganglia, and exhibited minimal replication.
- No reactivable latent infections were established in the trigeminal ganglion.
Conclusions:
- The characterized HSV-1 recombinants display a significantly attenuated phenotype in mice.
- These modified HSV-1 strains are essentially avirulent, non-neuroinvasive, and do not establish latent infections.
- The developed recombinant viruses represent a valuable tool for investigating HSV-1 pathogenesis and exploring novel therapeutic targets.