A HERPES-SIMPLEX VIRUS TYPE-1 ICP22 DELETION MUTANT IS ALTERED FOR VIRULENCE AND LATENCY IN-VIVO

The in vivo function of the herpes simplex virus type 1 immediate earl y gene ICP22 has been investigated in mice and guinea pigs using a del etion mutant (de122Z) of HSV-1(F) that lacks all but 18 nucleotides of the ICP22 coding sequence. This mutant carries the bacterial lacZ gen e at the site of the deletion and makes functional beta-galactosidase, but is unable to synthesize any detectable ICP22 messenger RNA or pro tein in vitro. De122Z was impaired in its ability to cause death in mi ce following intracerebral, intraperitoneal, or intravaginal inoculati on. The mutant failed to produce lesions or other visible signs of inf ection after bilateral corneal infection of mice but could be recovere d from trigeminal ganglia explanted at day 30 after inoculation. De122 Z replicated poorly after intravaginal inoculation of mice and guinea pigs in comparison to the parental virus, and was not recoverable from the dorsal root ganglia of either species. Nevertheless, de122Z seque nces could be detected in the dorsal root ganglia of guinea pigs at da y 30 by the polymerase chain reaction. These studies demonstrate that the ICP22 gene product is required for acute infection and virulence i n two standard in vivo animal models.