Biological Basis for Virulence of Three Strains of Herpes Simplex Virus Type 1

Abstract

Herpes simplex virus type 1 (HSV-1) strains F, HF and HFEM were studied with respect to pathogenicity in mice and growth characteristics in vivo and in vitro compared to the neurovirulent HSV-1 strains 17 syn+ and KOS. All three viruses demonstrated reduced virulence in mouse brains and were completely avirulent after footpad inoculation. They were shown to express high levels of thymidine kinase activity. Investigations concerning the virulence phenotype indicated that the defect(s) in strains F, HF and HFEM related to general replication deficiency in mouse cells. It was also shown that although the replication restriction observed for strains F and HF was specific for murine cells, strain HFEM did not replicate well in any cell type tested. Additional studies indicated that the avirulence phenotype which followed peripheral inoculation was related to different genotypes, since strain F complement HF and HFEM and, as expected, the latter two agents did not complement each other. All three agents were found to complement the non-neuroinvasive strain KOS. Finally, the data also show that two herpesviruses which are highly restricted in murine cells (e.g. strains F and HF) can still interact in the animal and produce a lethal infection.