Effect of eight antiviral drugs on the reactivation of herpes simplex virus in explant cultures of latently infected mouse trigeminal ganglia.
The effect of several antiviral drugs on the reactivation of herpes simplex virus type 1 in explant cultures of latently infected mouse trigeminal ganglia was investigated. Phosphonoacetate and phosphonoformate, which act directly on the virus-induced DNA polymerase, require a drug concentration of 400 micrograms/ml for the inhibition of virus reactivation in latently infected ganglia. Arabinosyladenine and arabinosyladenine monophosphate, which are phosphorylated to triphosphates by cellular enzymes and inhibit virus synthesis either by blocking the DNA polymerase or by incorporation into viral DNA, require a concentration of only 100 micrograms/ml for the inhibition of the reactivation process. Drugs that are phosphorylated by the virus-induced thymidine kinase, such as acyclovir, arabinosylthymine, bromovinyldeoxyuridine, and three fluorinated pyrimidine nucleosides require the lowest drug concentrations for complete inhibition of virus reactivation in latently infected ganglia explant cultures. Our data suggest that the inhibition of virus reactivation is dependent not only on drug concentration, but also on the number of latently infected neurons in the ganglia.
D000212:Acyclovir / Q000494:pharmacology; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D000998:Antiviral Agents / Q000494:pharmacology*; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives / Q000494:pharmacology; D001087:Arabinonucleosides / Q000494:pharmacology; D001973:Bromodeoxyuridine / Q000031:analogs & derivatives / Q000494:pharmacology; D003470:Culture Media; D046508:Culture Techniques; D003561:Cytarabine / Q000031:analogs & derivatives / Q000494:pharmacology; D017245:Foscarnet; D051379:Mice; D008812:Mice, Hairless; D009500:Neutralization Tests; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D018139:Simplexvirus / Q000254:growth & development* / Q000276:immunology / Q000302:isolation & purification; D013936:Thymidine / Q000031:analogs & derivatives / Q000494:pharmacology; D014276:Trigeminal Nerve / Q000382:microbiology; D001084:Vidarabine Phosphate / Q000494:pharmacology; D014775:Virus Activation / Q000187:drug effects*
D000914:Antibodies, Viral; D000998:Antiviral Agents; D001087:Arabinonucleosides; D003470:Culture Media; D003561:Cytarabine; D001084:Vidarabine Phosphate; C020235:brivudine; D001086:Arabinofuranosyluracil; D017245:Foscarnet; C026023:fiacitabine; C043457:fialuridine; D001973:Bromodeoxyuridine; C034935:clevudine; D010746:Phosphonoacetic Acid; C010032:thymine arabinoside; D013936:Thymidine; D000212:Acyclovir