title: A low thymidine kinase-producing mutant of herpes simplex virus type 1 causes latent trigeminal ganglia infections in mice.
abstract: 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.
mesh_terms: D000818:Animals; D001921:Brain / Q000382:microbiology; D005123:Eye / Q000382:microbiology; D006561:Herpes Simplex / Q000382:microbiology*; D051379:Mice; D009154:Mutation; D011149:Pons / Q000382:microbiology; D018139:Simplexvirus / Q000201:enzymology / Q000472:pathogenicity / Q000502:physiology*; D013937:Thymidine Kinase / Q000378:metabolism*; D012668:Trigeminal Ganglion / Q000382:microbiology*; D014276:Trigeminal Nerve / Q000382:microbiology*; D014774:Virulence; D014779:Virus Replication
chemical_list: D013937:Thymidine Kinase