Vanadate promotes reactivation and iontophoresis-induced ocular shedding of latent HSV-1 W in different host animals.
Vanadate is a potent inhibitor of calcium stimulated ATPase, Na, K-ATPase, and may have adrenergic activity. Using the iontophoresis method, we compared vanadate to a BSS control and the standard iontophoresis model (6-hydroxydopamine/epinephrine) by measuring induced ocular shedding of latent HSV-1 in different host animals. Latent trigeminal ganglionic infections were established in Balb/c mice and New Zealand rabbits following corneal inoculation with HSV-1 [W] strain, and later confirmed by cocultivation. Latently-infected animals (greater than 1 month post-infection) were divided into three treatment groups. Each group was iontophoresed with BSS, vanadate 1% or 6-HD 1%, and then treated topically for 10 days with BSS, vanadate or epinephrine respectively. Reactivation and recovery of latent HSV-1 was detected by daily ocular swabbing, plating, and observing progressive viral growth in Vero cells. The vanadate group had more virus-positive eyes than the BSS control group in mice, (8/32 vs. 1/32 P less than .01), and also in rabbits (14/20 vs 6/22 P less than .01). Virus-positive animals and total positive swabs were also higher for vanadate than BSS in both mice and rabbits. Furthermore, while vanadate was associated with fewer virus-positive eyes than 6-HD & EPI (8/32 vs. 17/32 P less than .02) in mice, there were no significant differences in rabbits. We conclude that vanadate promotes ocular shedding of latent HSV-1, and may act through an adrenergic mechanism.
Gordon
Y J
YJ
Eye and Ear Institute of Pittsburgh, PA.
Romanowski
E
E
Berman
J
J
Vikoren
P
P
Lin
L S
LS
Schlessinger
D
D
Araullo-Cruz
T
T
D000818:Animals; D002478:Cells, Cultured; D016009:Chi-Square Distribution; D003315:Cornea / Q000382:microbiology; D004837:Epinephrine / Q000494:pharmacology; D005123:Eye / Q000382:microbiology*; D005260:Female; D006892:Hydroxydopamines / Q000494:pharmacology; D007478:Iontophoresis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016627:Oxidopamine; D011817:Rabbits; D018139:Simplexvirus / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification; D013666:Tears / Q000382:microbiology; D012668:Trigeminal Ganglion / Q000382:microbiology; D014638:Vanadates / Q000494:pharmacology*; D014709:Vero Cells; D014775:Virus Activation / Q000187:drug effects*; D014776:Virus Cultivation
D006892:Hydroxydopamines; D014638:Vanadates; D016627:Oxidopamine; D004837:Epinephrine