IMR Press / FBL / Volume 1 / Issue 1 / DOI: 10.2741/A106

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Deletion of the Herpes simplex 1 internal repeat sequences affects pathogenicity in the mouse
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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
2 Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD. 20814
3 Food and Drug Administration, Division of Antiviral Drug Products, Rockville, MD 20857
Academic Editor:Frank Jenkins
Front. Biosci. (Landmark Ed) 1996, 1(1), 59–68;
Published: 4 October 1996
(This article belongs to the Special Issue Human viruses and cancer)

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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