No abstract

The susceptibility of mice of different ages (from four to 28 days) to infection with herpes simplex virus type 1 (HSV-1) mutants inoculated onto scarified corneas was studied. The TK+ isolate from wild type virus was pathogenic in mice of all age groups. An HSV-1 mutant (designated TK1/4) with a less active thymidine kinase (TK) gene expressing 25 per cent of the TK activity of the TK+ isolate was pathogenic for mice up to 10 days of age. In older mice, virus pathogenicity was dependent on the inoculum dose: increasing the TK1/4 virus dose tenfold raised the level of TK activity and thus the virulence of the virus. A TK- mutant with no TK activity was pathogenic for four to eight day old mice that have TK activity in the brain, but not in older mice. Thus, resistance to HSV-1 that is age-dependent in mice can be determined by the extent to which the virus strain is liable to express its TK gene and by the amount of TK activity present in the brain.

The wild type NIH strain of herpes simplex virus type 1 (HSV-1) has a mixed plaque morphology of both large and small plaques. From this virus we selected a large plaque isolate that was a high producer of thymidine kinase (TK) activity (designated TK+) and a small plaque isolate that produced 25 per cent of the TK activity of the large plaque mutant (designated TK 1/4). A TK- mutant of the large plaque virus was obtained after passage of the virus in the presence of BUdR. The pathogenicity of the TK 1/4 virus strain in relation to the TK+ and TK- strains was investigated in mice after inoculation of the virus into the eyes by corneal scarification. The TK+ strain was highly pathogenic, caused encephalitis and killed most of the mice, whereas the TK- strain did not cause latent infections in the trigeminal ganglia or kill the mice. The TK 1/4 virus strain replicated in the eyes within 24 hours after inoculation and entered the trigeminal ganglia, establishing a latent infection in almost all of the mice. By increasing the infectious dose tenfold, the TK 1/4 virus caused an active infection in the trigeminal ganglia (ganglionitis), migrated to the brain, and killed the mice. The results indicate that not only is a low level of TK required to establish latent infections in mice, but also the degree of virulence is determined by the amount of TK produced by the infecting virus.

No abstract

Autoclaves used for sterilization and decontamination of biological materials operate at temperatures of 121°C or higher.