Inhibition of cyclooxygenase 2 synthesis suppresses Herpes simplex virus type 1 reactivation

J Ocul Pharmacol Ther. 2005 Apr;21(2):114-20. doi: 10.1089/jop.2005.21.114.


Recurrent herpes virus infection, in which the virus reactivates from the nervous system and causes painful lesions in peripheral tissues, is a significant clinical problem. Our recent studies showing that the amount of cyclooxygenase 2 (COX-2) in the trigeminal ganglia of heat-stressed untreated mice is higher than the amount in heat-stressed mice treated with the COX-2 inhibitor, celecoxib, have indicated that the prostaglandin synthesis pathway--and in particular COX-2--may be an intermediate in the pathway to herpes viral reactivation. To further study this process, we infected the corneas of mice using topical application to a lightly scratched epithelium and waited 30 days for Herpes simplex virus type 1 (HSV-1) latency to be established in the trigeminal ganglia. Prior to the induction of viral reactivation, the mice were treated orally with celecoxib. Treated and untreated mice were induced to undergo reactivation by immersion in 43 degrees C water for 10 min. The shedding of virus at the ocular surface was determined by culturing ocular swabs with indicator cells. The presence of infectious virus in the trigeminal ganglion was evaluated by incubating ganglion homogenates with indicator cells and observing for cytopathic effect. Celecoxib treatment significantly suppressed viral reactivation when given prophylactically by the gastrointestinal route. The numbers of corneas and ganglia containing infectious virus were significantly lower in the celecoxib-treated animals, compared to the placebo-treated mice. These experiments demonstrate that a selective COX-2 inhibitor can suppress hyperthermic stress-induced herpes viral reactivation in the nervous system. It may be possible to use COX-2 inhibitors to prevent viral reactivation in high-risk patients by drug prophylaxis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Celecoxib
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / therapeutic use*
  • Disease Models, Animal
  • Female
  • Heat Stress Disorders / enzymology
  • Heat Stress Disorders / virology
  • Herpesvirus 1, Human / drug effects*
  • Herpesvirus 1, Human / physiology
  • Keratitis, Herpetic / enzymology
  • Keratitis, Herpetic / virology*
  • Mice
  • Mice, Inbred BALB C
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Pyrazoles / therapeutic use*
  • Secondary Prevention
  • Sulfonamides / therapeutic use*
  • Trigeminal Ganglion / virology
  • Virus Activation / drug effects*


  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Pyrazoles
  • Sulfonamides
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Celecoxib