A low thymidine kinase-producing mutant of herpes simplex virus type 1 causes latent trigeminal ganglia infections in mice

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Abstract
Summary 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.