ACYCLOVIR BLOCKS CYTOKINE GENE-EXPRESSION IN TRIGEMINAL GANGLIA LATENTLY INFECTED WITH HERPES-SIMPLEX VIRUS TYPE-1

We have previously found that interleukin (IL)-2, IL-10, interferon (I FN)-gamma, RANTES, and tumor necrosis factor (TNF)-gamma mRNA transcri ption remain elevated in the trigeminal ganglia (TG) of herpes simplex virus type 1 (HSV-I) latently infected mice up to 120 days postinocul ation (p.i.). To determine if this phenomenon was dependent on HSV-1 D NA replication after the establishment of latency (i.e., reactivation) , cytokine gene expression was compared in TG of acyclovir-treated and untreated latently infected mice. Oral acyclovir treatment (begun 16 days p.i.) had no effect on serum levels of total anti-HSV-l antibodie s. However, there was a significant reduction in the titer of antibody specific for glycoprotein D and glycoprotein B but not glycoprotein H /L 120 days PI in the acyclovir-treated compared to vehicle-treated mi ce. These differences were not significant at earlier time points (i.e ., days 34 and 60 p.i.). Consistent with these findings, acyclovir had no effect on cytokine gene expression in latently infected TG 35 and 60 days p.i. However, 120 days p.i., IFN-gamma and TNF-alpha mRNA were approaching baseline levels in TG of acyclovir-treated mice, but rema ined significantly elevated in untreated controls (i.e., IFN-gamma mRN A levels were sixfold higher in TG of untreated mice). Therefore, vira l DNA replication appears to provide an antigenic stimulus for persist ent cytokine gene expression in latently infected TG. (C) 1997 Academi c Press.