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 immunologic nitric oxide synthase (iNOS) within brains of 42 HSV-1 F infected mice was studied by using a titration PCR assay for HSV-1 DNA and a semiquantitative 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 encephalitis (HSVE). Following infection, a parallel increase of iNOS mRNA and HSV-1F-DNA occurred with peaks after 7 days that were both significantly lower under acyclovir treatment. Six months post infection viral load had declined, but iNOS mRNA expression in both treated and untreated mice was still enhanced as compared with mock infected controls. This suggests that acyclovir decreases iNOS expression via inhibition of viral replication shortly after infection but fails to influence elevated iNOS within the brain late in the course of experimental HSVE.
D000212:Acyclovir / Q000627:therapeutic use*; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D001921:Brain / Q000201:enzymology / Q000821:virology; D004279:DNA, Viral / Q000378:metabolism; D004660:Encephalitis / Q000821:virology*; D005260:Female; D006561:Herpes Simplex / Q000188:drug therapy*; D018259:Herpesvirus 1, Human / Q000235:genetics; D007158:Immunologic Techniques; D051379:Mice; D008815:Mice, Inbred Strains; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D012333:RNA, Messenger / Q000378:metabolism; D012016:Reference Values; D013997:Time Factors; D019562:Viral Load