Acyclovir treatment of experimentally induced herpes simplex virus encephalitis: monitoring the changes in immunologic NO synthase expression and viral load within brain tissue of SJL mice

The effect of acyclovir treatment on viral burden and the expression of imm unologic nitric oxide synthase (iNOS) within brains of 42 HSV-1F infected m ice was studied by using a titration PCR assay for HSV-1 DNA and a semiquan titative RT-PCR for iNOS mRNA. iNOS mediated NO-production may possibly be involved in secondary mechanisms of brain injury following virus infection, which may account for treatment failures in human herpes simplex virus enc ephalitis (HSVE). Following infection, a parallel increase of iNOS mRNA and HSV-1F-DNA occurred with peaks after 7 days that were both significantly l ower under acyclovir treatment. Six months post infection viral load had de clined, but iNOS mRNA expression in both treated and untreated mice was sti ll enhanced as compared with mock infected controls. This suggests that acy clovir decreases iNOS expression via inhibition of viral replication shortl y after infection but fails to influence elevated iNOS within the brain lat e in the course of experimental HSVE. (C) 1999 Elsevier Science Ireland Ltd . All rights reserved.