Herpes Simplex Virus Type 2 UL24 Gene Is a Virulence Determinant in Murine and Guinea Pig Disease Models

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Abstract
A herpes simplex virus type 2 (HSV-2) UL24 β-glucuronidase (UL24-βgluc) insertion mutant was derived from HSV-2 strain 186 via standard marker transfer techniques. Cell monolayers infected with UL24-βgluc yielded cytopathic effect with syncytium formation. UL24-βgluc replicated to wild-type viral titers in three different cell lines. UL24-βgluc was not virulent after intravaginal inoculation of BALB/c mice in that all inoculated animals survived doses up to 400 times the 50% lethal dose (LD 50 ) of the parental virus. Furthermore, few UL24-βgluc-inoculated mice developed any vaginal lesions. Intravaginal inoculation of guinea pigs with UL24-βgluc at a dose equivalent to the LD 50 of parental virus (≈5 × 10 3 PFU) was not lethal (10/10 animals survived). Although genital lesions developed in some UL24-βgluc-inoculated guinea pigs, both the overall number of lesions and the severity of disease were far less than that observed for animals infected with parental strain 186.