Prophylactic acyclovir effectively reduces herpes simplex virus type 1 reactivation after exposure of latently infected mice to ultraviolet B.
OBJECTIVE
To determine the potential efficacy and anatomic sites of action of prophylactic oral acyclovir using a murine model of ultraviolet-B-induced reactivation of herpes simplex 1 keratitis.


METHODS
Latent infection with herpes simplex 1 (McKrae) was established in 80 National Institutes of Health inbred strain of mice. Forty of the mice were given acyclovir orally and the other 40 latently infected mice served as controls. Mice were exposed to 250 mJ/cm2 of ultraviolet-B radiation and killed on days 1, 2, 3, and 4 after ultraviolet-B radiation. Trigeminal ganglia and eyes from these mice were homogenized and incubated on Vero cell monolayers for recovery of reactivated virus.


RESULTS
Based on the recovery of infectious virus after ultraviolet-B in treated versus control groups, acyclovir effectively reduced detectable viral reactivation at both the ocular level (P = 0.003) and the ganglionic level (P = 0.025). The numbers of viral culture-positive eye and trigeminal ganglia homogenates in the control group were 11 and 6 out of 40, respectively, compared to 1 and 0 out of 40 culture-positive eye and trigeminal ganglia homogenates in the acyclovir treated mice. Therapeutic serum levels of acyclovir were confirmed by high performance liquid chromatography. In the acyclovir-tested group, the single case of viral break-through at the ocular surface was not an acyclovir-resistant mutant.


CONCLUSIONS
Prophylactic acyclovir effectively reduces the incidence of herpes simplex virus-1 reactivation after ultraviolet-B-induced reactivation in National Institutes of Health inbred strain of mice.
Blatt
A N
AN
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110.
Laycock
K A
KA
Brady
R H
RH
Traynor
P
P
Krogstad
D J
DJ
Pepose
J S
JS
D000212:Acyclovir / Q000008:administration & dosage* / Q000097:blood; D000284:Administration, Oral; D000818:Animals; D003315:Cornea / Q000294:innervation / Q000382:microbiology; D004195:Disease Models, Animal; D005260:Female; D018259:Herpesvirus 1, Human / Q000254:growth & development* / Q000302:isolation & purification; D016849:Keratitis, Herpetic / Q000097:blood / Q000517:prevention & control*; D051379:Mice; D008815:Mice, Inbred Strains; D011292:Premedication; D014466:Ultraviolet Rays; D014709:Vero Cells; D014775:Virus Activation / Q000187:drug effects* / Q000528:radiation effects
D000212:Acyclovir