<i>In vivo </i>Characteristics of Temperature-Sensitive Host Range Mutants of Herpes Simplex Virus Type 2

Abstract

The in vivo properties of four host range temperature-sensitive (ts) mutants of herpes simplex virus type 2 (HSV-2) were correlated with known in vitro characteristics. Mutants and parental virus were inoculated into newborn and weanling mice and weanling hamsters by intracranial and subcutaneous routes, and into weanling rabbits by corneal scarification. In all cases the pattern of attenuation of mutants in vivo correlated with their stability in vitro at 39°. The most attenuated mutant (mutant 69) was also the most consistent in its inability to induce cytopathic effects (CPE) in vitro or to replicate under nonpermissive conditions. Conversely, the most virulent mutant (mutant 41) was the least stable under nonpermissive conditions.

Host range temperature-sensitive mutants of herpes simplex virus type 2

“…Taken together, the data on the transforming potential of the three viruses tested lead to the conclusion that great care must be exercised in the development of attenuated herpes simplex virus vaccines. Mutant 74 is attenuated, both for growth in cell culture and for virulence in mice (22), and on this criterion would be considered a suitable vaccine candidate. However, by selecting for growth attenuation, selection has also been made for a virus whose cytolytic properties are more than usually sensitive to exogenous damage, but whose transforming capabilities remain intact.…”

“…and passaged only in human cells, was the parental wild-type HSV-2 used in this study. Two mutants of HSV-2 strain 333, whose isolation and preliminary characterization have been reported recently (22)(23)(24), were examined. One mutant (no.…”