Mutation of the herpes simplex virus 1 KOS UL45 gene reveals dose dependent effects on central nervous system growth

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, UL45A, 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 x 10(3) pfu were injected intracerebrally into Balb/c mice. In contrast, at inocula greater than 1 x 10(3), the UL45 mutants were lethal. In vivo growth curves derived from mice inoculated intracerebrally with 1 x 10(3) 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.