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 early gene ICP22 has been investigated in mice and guinea pigs using a deletion mutant (del22Z) of HSV-1(F) that lacks all but 18 nucleotides of the ICP22 coding sequence. This mutant carries the bacterial lacZ gene at the site of the deletion and makes functional beta-galactosidase, but is unable to synthesize any detectable ICP22 messenger RNA or protein in vitro. Del22Z was impaired in its ability to cause death in mice following intracerebral, intraperitoneal, or intravaginal inoculation. The mutant failed to produce lesions or other visible signs of infection after bilateral corneal infection of mice but could be recovered from trigeminal ganglia explanted at day 30 after inoculation. Del22Z 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, del22Z sequences could be detected in the dorsal root ganglia of guinea pigs at day 30 by the polymerase chain reaction. These studies demonstrate that the ICP22 gene product is required for acute infection and virulence in two standard in vivo animal models.
Poffenberger
K L
KL
Syntex Research, Palo Alto, California.
Idowu
A D
AD
Fraser-Smith
E B
EB
Raichlen
P E
PE
Herman
R C
RC
D000818:Animals; D002522:Chlorocebus aethiops; D003315:Cornea / Q000821:virology; D004268:DNA-Binding Proteins; D005260:Female; D005727:Ganglia, Spinal / Q000821:virology; D017353:Gene Deletion; D006168:Guinea Pigs; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D013997:Time Factors; D014162:Transfection; D014276:Trigeminal Nerve / Q000821:virology; D014621:Vagina / Q000821:virology; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics*; D014774:Virulence; D017735:Virus Latency; D017201:Virus Shedding
D004268:DNA-Binding Proteins; C045462:ICP8 protein, Simplexvirus; D014764:Viral Proteins