A temporal analysis of acyclovir inhibition of induced herpes simplex virus type 1 in vivo reactivation in the mouse trigeminal ganglia

It is generally assumed that reactivation of latent herpes simplex virus oc curs through initiation of lytic viral gene transcription from the latent v iral genome. Thus, antiviral compounds such as acyclovir, whose activation is dependent upon viral thymidine kinase, should be effective in preventing the initial production of infectious virus associated with reactivation. T o test this concept, the ability of acyclovir to prevent the production of infectious virus was determined in the murine hyperthermic stress (HS) mode l of in vivo reactivation. Acyclovir treatment after HS blocked the product ion of infectious virus within the ganglia, Efficacy was dependent upon the timing of the first post-HS dose and the length of exposure to acyclovir, A single dose administered 6-9 h after HS resulted in >90% reduction in rea ctivation. Acyclovir administered 12 h after HS resulted in 75% reduction, but there was no effect if treatment was delayed for 18 h after HS.