Open Access
Article
Deletion of the Herpes simplex 1 internal repeat sequences affects pathogenicity in the mouse
F J Jenkins1,A M Donoghue1,J R Martin1
1
Department 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
DOI: 10.2741/A106 Volume 1 Issue 1, pp.59-68
Published: 04 October 1996
(This article belongs to the Special Issue Human viruses and cancer)
Abstract

We have isolated three different herpes simplex virus 1 (HSV-1) recombinant viruses, each frozen in either the P (prototype), IS (inversion of S component), or ILS (inversion of both components) genome arrangement. Common to all three recombinant viruses is the deletion of approximately 14 kilobases (kb) of viral DNA sequences representing greater than 95% of the internal repeat sequences and the insertion of a 9.6 kb mini-Mu genome containing a functional thymidine kinase gene. No unique DNA sequences were deleted from the viral genomes. Analyses of growth curves of the wild-type and recombinant viruses in cell culture has revealed that the recombinants grow somewhat more slowly, producing final titers within 1.5 logs of wild-type HSV-1(F). There is no discernible difference in plaque size or plaque morphology between the recombinant and wild type strains. Analysis of the recombinant viruses in mice reveals the following: I), the recombinant viruses are essentially avirulent, exhibiting drastically increased LD50 values as compared to the wild-type strain by intracerebral injection; ii), the recombinant viruses are not neuroinvasive in that they do not spread from the cornea to sensory ganglion; iii), the recombinant viruses exhibit minimal local replication both in the corneas of infected mice and in the brains of mice inoculated by intracerebral injection; and iv), the recombinant viruses do not establish a reactivable latent infection in the trigeminal ganglion following either intracerebral inoculation or inoculation of scarified corneas. These properties suggest a unique pattern of pathogenesis for HSV mutants in the mouse model.

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F J Jenkins, A M Donoghue, J R Martin. Deletion of the Herpes simplex 1 internal repeat sequences affects pathogenicity in the mouse. Frontiers in Bioscience-Landmark. 1996. 1(1); 59-68.