In vivo epinephrine reactivation of ocular herpes simplex virus type 1 in the rabbit is correlated to a 370-base-pair region located between the promoter and the 5' end of the 2.0 kilobase latency-associated transcript.
A rabbit ocular model of epinephrine-induced herpes simplex virus type 1 reactivation was employed to study the effect of a deletion in the latency-associated transcript domain. A viral construct derived from 17Syn+, designated 17deltaSty, has a deletion of 370 nucleotides between genomic positions 118880 and 119250. 17deltaSty has been shown to reactivate with wild-type virus kinetics from explants of trigeminal ganglia from latently infected mice. To determine the behavior of this mutant in an in vivo, inducible reactivation system, rabbit corneas were infected with 17Syn+, 17deltaSty, or its rescuant, 17detlaSty-Res. After viral latency was established, transcorneal epinephrine iontophoresis was performed. The rabbits latently infected with 17deltaSty exhibited a significantly reduced ability to undergo adrenergically induced reactivation, i.e., viral shedding in the tears, compared with rabbits infected with either 17Syn+ or 17deltaSty-Res. However, quantitative PCR demonstrated similar numbers of viral genomes in the trigeminal ganglia from rabbits latently infected with all three viruses, and all three viruses reactivated in vitro with wild-type kinetics in an explant cocultivation assay. These studies indicate that the 370-bp region deleted in the 17deltaSty construct plays a role in epinephrine-induced reactivation.
Hill
J M
JM
LSU Eye Center, Louisiana State University Medical Center School of Medicine, New Orleans, Louisiana 70112-2234, USA.
Maggioncalda
J B
JB
Garza
H H
HH
Su
Y H
YH
Fraser
N W
NW
Block
T M
TM
D000818:Animals; D002478:Cells, Cultured; D004837:Epinephrine / Q000494:pharmacology; D015828:Eye Infections, Viral; D006561:Herpes Simplex / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000502:physiology*; D051379:Mice; D012367:RNA, Viral; D011817:Rabbits; D013566:Sympathomimetics / Q000494:pharmacology; D014158:Transcription, Genetic; D014775:Virus Activation / Q000187:drug effects / Q000235:genetics*; D017735:Virus Latency / Q000235:genetics*
D012367:RNA, Viral; D013566:Sympathomimetics; D004837:Epinephrine