Differential effects of famciclovir and valaciclovir on the pathogenesis of herpes simplex virus in a murine infection model including reactivation from latency.
The ability of famciclovir and valaciclovir to affect the establishment and maintenance of latency in mice with a cutaneous herpes simplex type 1 (HSV-1) infection was examined. Mice were treated via drinking water starting at various times between days 1 and 5 and terminating on day 10 after inoculation. Clinical signs and viral replication in the target tissues were monitored. Three to four months later, trigeminal and dorsal root ganglia were explanted from groups of 16 mice and examined for latent virus by cocultivation. The two compounds differed in their effects on the acute neural infection, and ganglia explanted from famciclovir-treated mice were markedly reduced in their ability to reactivate virus, although neither drug affected latency if treatment was delayed for several months. The difference between the compounds is likely to reflect differences in the metabolism of their respective products, penciclovir and acyclovir, in infected neurons.
Thackray
A M
AM
Centre for Research in Veterinary Science, Cambridge University Veterinary School, United Kingdom.
Field
H J
HJ
D015075:2-Aminopurine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000208:Acute Disease; D000212:Acyclovir / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001933:Brain Stem / Q000821:virology; D004195:Disease Models, Animal; D004431:Ear, External / Q000821:virology; D000077595:Famciclovir; D005260:Female; D005727:Ganglia, Spinal / Q000821:virology; D006561:Herpes Simplex / Q000188:drug therapy / Q000401:mortality / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D011355:Prodrugs / Q000494:pharmacology* / Q000627:therapeutic use; D012668:Trigeminal Ganglion / Q000821:virology; D000077483:Valacyclovir; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D014775:Virus Activation / Q000187:drug effects / Q000502:physiology; D017735:Virus Latency / Q000187:drug effects / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology
D000998:Antiviral Agents; D011355:Prodrugs; D015075:2-Aminopurine; D014633:Valine; D000077483:Valacyclovir; D000077595:Famciclovir; D000212:Acyclovir