Mutation of the herpes simplex virus 1 KOS UL45 gene reveals dose dependent effects on central nervous system growth |
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Authors: | R J Visalli C R Brandt |
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Institution: | (1) Department of Medical Microbiology and Immunology, University of Wisconsin Medical School, Madison, Wisconsin, U.S.A., US;(2) Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical School, Madison, Wisconsin, U.S.A., US |
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Abstract: | Summary. The herpes simplex virus type 1 (HSV-1) UL45 gene encodes an 18 kDa virion envelope protein whose function remains unknown.
Previous studies using a UL45 null mutant, UL45Δ, demonstrated that deletion of the UL45 gene altered plaque size in Vero
and HeLa cells, but was not essential for replication in these cell types. The goal of this study was to determine if mutation
of the UL45 gene influenced virus growth in the CNS. Two UL45 mutants, as well as a repaired revertant virus, were constructed
and tested for their ability to cause encephalitis and replicate in the CNS. The UL45 mutants were not lethal when 1 × 103 pfu were injected intracerebrally into Balb/c mice. In contrast, at inocula greater than 1 × 103, the UL45 mutants were lethal. In vivo growth curves derived from mice inoculated intracerebrally with 1 × 103 pfu of virus revealed that the mutants grew poorly compared to wild type or revertant viruses. These results suggest that
the 18 kDa UL45 gene product is required for efficient growth in the central nervous system at low doses. We propose that
the UL45 gene may play an important role under the conditions of a naturally acquired infection.
Received June 23, 2001 Accepted November 1, 2001 |
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