Synergistic antiviral activities of acyclovir and recombinant human leukocyte (alpha) interferon on feline herpesvirus replication.
The antiviral activities of 9-(2-hydroxyethoxymethyl)guanine (acyclovir; ACV) either alone or combined with recombinant human leukocyte (alpha) A/D interferon (rHuIFN-alpha) against feline herpesvirus type 1 (FHV-1) were evaluated in feline embryo cell cultures, using an infectivity-inhibition assay. In ACV-treated cultures, the 50% inhibitory dose (ID50) was approximately 10 to 20 micrograms of ACV/ml. Maximal inhibition of FHV-1 infectivity (range, 3.4 to 4.2 log10 TCID50) was observed when high test doses of ACV (125 or 250 micrograms/ml) were given 1 to 6 hours after infection. Although mild inhibition (range, 0.3 to 1.6 log10 TCID50) of virus was observed at lower drug doses (10 to 62.5 micrograms/ml), FHV-1 was relatively resistant to ACV and required higher minimal inhibitory doses than those reported for other herpesviruses. However, when ACV was combined with 10 or 100 U of rHuIFN-alpha/ml, synergistic antiviral effects were associated with ACV dosage of 10 to 62.5 micrograms/ml. Antiviral activities resulting from use of the combined drugs permitted nearly eightfold reduction in the dose of ACV required to achieve maximal inhibition of FHV-1. Significant (P less than 0.01) synergistic interactions with ACV resulted when the rHuIFN-alpha was given before or after infection; at the lower doses of ACV, however, rHuIFN-alpha pretreatment was more effective. Although dosages of either greater than or equal to 62.5 micrograms of ACV/ml or 100 U of rHuIFN-alpha/ml were cytosuppressive in control cell cultures, additive anticellular effects were not observed at synergistic combinations of ACV and 10 U of rHuIFN-alpha/ml.
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Scott Ritchey Research Program, College of Veterinary Medicine, Auburn University, AL 36849-3501.
D000212:Acyclovir / Q000494:pharmacology*; D000818:Animals; D002371:Cat Diseases / Q000382:microbiology; D002415:Cats; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006564:Herpesviridae / Q000187:drug effects* / Q000502:physiology; D006566:Herpesviridae Infections / Q000382:microbiology / Q000662:veterinary; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D011994:Recombinant Proteins; D012141:Respiratory Tract Infections / Q000382:microbiology / Q000662:veterinary; D014779:Virus Replication / Q000187:drug effects*
D007370:Interferon Type I; D011994:Recombinant Proteins; D000212:Acyclovir