Effect of acyclovir on thermal stress-induced herpesvirus reactivation.
OBJECTIVE
Acyclovir has been shown to be effective in preventing recurrent herpes simplex virus lesions of the genitalia and oral labia. The purpose of the current study was to determine the effect of acyclovir on the appearance of infectious virus in the peripheral nervous system and in an end organ, the eye.


METHODS
Mice latent for the McKrae strain of herpes simplex virus type 1 were given 3.5 mg/ml acyclovir in their drinking water. Control animals received water without drug. Acyclovir treatment was continued for 4 successive days. On the third day, the mice were subjected to a brief period of hyperthermic stress to induce viral reactivation. Twenty-four hours after stress induction, swabs of the ocular surface and homogenates of the cornea and trigeminal ganglia were analyzed for the presence of infectious herpes simplex virus type 1 and viral DNA.


RESULTS
Acyclovir treatment significantly decreased the frequency of infectious virus in the ocular tear film and the cornea but not in the trigeminal ganglion. The corneal homogenates of acyclovir-treated animals contained smaller amounts of viral DNA compared with untreated controls, whereas the amounts of viral DNA in the trigeminal ganglia of acyclovir-treated and untreated animals were similar.


CONCLUSIONS
These results suggest that oral administration of acyclovir, at least at the dose used in this study, is effective in modestly reducing viral replication in peripheral tissues such as the eye but is not effective in inhibiting viral reactivation and viral DNA synthesis in the peripheral nervous system in mice subjected to induction of reactivation by hyperthermic stress.
Gebhardt
Bryan M
BM
Lions Eye Research Laboratories, LSU Eye Center, Louisiana State University Health Sciences Center, 2020 Gravier Street, New Orleans, LA 70112-2234, USA. bgebha@lsuhsc.edu
Kaufman
Herbert E
HE
Hill
James M
JM
D000212:Acyclovir / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D003315:Cornea / Q000378:metabolism / Q000821:virology; D004279:DNA, Viral / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D005123:Eye / Q000821:virology; D005260:Female; D018882:Heat Stress Disorders / Q000378:metabolism / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000502:physiology*; D016849:Keratitis, Herpetic / Q000378:metabolism / Q000821:virology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010525:Peripheral Nerves / Q000821:virology; D013666:Tears / Q000821:virology; D012668:Trigeminal Ganglion / Q000378:metabolism / Q000821:virology; D014775:Virus Activation / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D004279:DNA, Viral; D000212:Acyclovir