The Comparative Effects of Famciclovir and Valacyclovir on Herpes Simplex Virus Type 1 Infection, Latency, and Reactivation in Mice

Abstract

Infections by herpes simplex virus (HSV) cannot yet be eliminated, but the severity of the disease can be reduced. Two newer drugs with established efficacy for such infections, famciclovir and valacyclovir, were tested in a mouse eye model of HSV infection. Both drugs significantly reduced mortality and titers of virus shed from the eyes of mice infected with an otherwise lethal dose of HSV type 1 (HSV-1). Similar titers of HSV-1 were found in the eyes, ganglia, and brains of treated animals. Although valacyclovir reduced the latent viral DNA load better in these studies than did famciclovir, rates of reactivation by explantation and UV exposure were the same. Thus, in this study, famciclovir and valacyclovir were equally effective in limiting the virulence and spread of HSV-1, despite their biochemical and pharmacologic differences.

Alpha/Beta Interferon and Gamma Interferon Synergize To Inhibit the Replication of Herpes Simplex Virus Type 1

“…The potency with which IFN-␤ and IFN-␥ inhibited HSV-1 replication in vivo appeared to be considerably greater than is typically achieved when animals are treated with ACV or other antiviral agents in vivo (12,18,30,36,58). In mice pretreated with IFN-␤ and IFN-␥, HSV-1 replication was not detected in the eyes of six of the eight mice, and the average level of virus replication in the remaining two mice was ϳ500-fold less than observed in vehicle-treated controls.…”

Axonal Transport and Sorting of Herpes Simplex Virus Components in a Mature Mouse Visual System

“…The drug was supplied ad libitum until the animals were sacrificed. This drug is normally prescribed for human patients and is known from previous studies to have no harmful effect in mice that are treated with it (8,21). Our experimental goal was to "pulse infect" with HSV by allowing the virus to replicate for the first 24 h of the experiment and then to block further viral replication in the animal.…”

“…To simplify the analysis, we used the oral prodrug of acyclovir, valacyclovir, to inhibit viral replication in glial cells in the optic nerve (21). Valacyclovir is a guanine analogue that acts within a few hours by interfering with viral DNA synthesis and thereby blocking viral replication and protein expression (19).…”

Gamma Interferon Impedes the Establishment of Herpes Simplex Virus Type 1 Latent Infection but Has No Impact on Its Maintenance or Reactivation in Mice

“…4). Virus titration was performed at indicated time points following infection by tissue homogenization and dilution on duplicate Vero cell monolayers (17). Thus, in both mouse strains, the ability of the control animals to elaborate IFN-␥ appeared to play no role in further attenuating the local infection in the eye or viral neuroinvasiveness.…”