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

Abstract

SUMMARYHerpes 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-I 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 complemented 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.

ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties

“…To test this hypothesis, two clinical strains of HSV1, strains BL1 and JS1, were isolated from cold sores from otherwise healthy volunteers (see above) and tested for tumour cell killing in vitro as compared to a standard laboratory strain of HSV1, strain 17+. 17+ is the most virulent of the strains of HSV on which oncolytic versions of the virus have previously been based, 29,30 and thus strain 17+ was chosen as an appropriate control against which to compare. This showed (Figure 2a) that in all the tumour cell lines tested, both BL1 and JS1 gave superior tumour cell killing as compared to strain 17+.…”

HSV-1 Neuroinvasiveness

“…In other experiments, using KOS as a 'baseline' agent, we assessed the neuroinva sive capacity of 3 other HSV-l virus strains [9]. As table 4 indicates, neither strains F, HF, nor HFEM were neuroinvasive when em ployed singly, but all pairwise combinations except for HF X HFEM demonstrated the phenotype.…”

Neuroinvasion by herpes simplex virus. An in vitro model for characterization of neurovirulent strains

“…Analyses of gel patterns of structural polypeptides of HSV type 1 strains have failed to identify neurovirulent strains (Pereira et al, 1976) and early reports of restriction enzyme analysis could not disclose any common genetic similarity between strains isolated from cases of encephalitis Hammer et al, 1980;Whitley et al, 1982). However recombination of avirulent strains in mice will generate virulent, lethal recombinants (Javier et al, 1986;Sedarati & Stevens, 1987). Also, intertypic recombinants can yield neurovirulent combinations, although most of such recombinants appear to be attenuated independently of the degree of virulence demonstrated by parental strains, suggesting a multigenetic control (Halliburton et al, 1987).…”