An acyclovir-resistant strain of herpes simplex virus type 2 which is highly virulent for mice

Herpes simplex virus type 2 (HSV-2), strain YS-4 C-1, isolated by plaque cloning from a clinical isolate was found to be resistant to acyclovir (ACV; acycloguanosine) in vitro. It was sensitive to phosphonoacetic acid and 9-beta-D-arabinofuranosyladenine. Thymidine kinase (TK) activity of YS-4 C-1 was less than 1% of that of other strains from the same clinical source. However, thymidine plaque autoradiography showed that YS-4 C-1 was not completely deficient in TK activity. YS-4 C-1 showed high virulence for mice like other HSV-2 strains which were sensitive to ACV. YS-4 C-1 was able to establish latent infection in mice. Virus isolated from the brain of a mouse died after being inoculated with YS-4 C-1 was also resistant to ACV. ACV was not effective in mice inoculated with YS-4 C-1. This study shows that not all ACV-resistant strains are avirulent for mice.