Two thymidine kinase deficient herpes simplex viruses exhibit unexpected virulence properties

Herpes simplex virus type 1 (HSV-1) strains ANG and ANG path expressed very low levels of thymidine kinase activity, and their replication in vitro was not significantly inhibited by arabinofuranosyl-thymine. However, after intracranial inoculation of mice, ANG and ANG path demonstrated median lethal doses and brain replication profiles that resembled the fully neurovirulent thymidine kinase positive strain 17 syn+. In short, ANG and ANG path demonstrated the neurovirulence characteristics of standard HSV strains that express high levels of thymidine kinase activity. In an extension of the pathogenesis studies, ANG path resembled 17 syn+ and killed mice after rear footpad inoculation. ANG, by contrast, did not kill after rear footpad inoculation. Thus, ANG path demonstrated neuroinvasiveness while ANG was apparently non-neuroinvasive. The significance of these results as they pertain to genes involved in pathogenesis is discussed.