Effect of Herpesvirus Inhibition on Primary SIV Infection in Cynomolgus Monkeys

Abstract

Foscarnet and (-)9-[4-hydroxy-2-(hydroxymethyl)butyl] guanine (H2G) have already been shown to inhibit herpesviruses in vitro and also to inhibit viral antigen production in primary SIV infection in monkeys. Attempts have been made to determine if these invivo effects on SIV were due to a direct effect on SIV or were mediated through inhibition of endogenous transactivating herpesviruses. The possible involvement of herpesviruses in primary SIVsrn infection in monkeys was studied by the use of various inhibitors of herpesvirus replication.Subcutaneous injections of 3 x 5 mg kg-1 day-1 of aciclovir, 3 x 5 mg kg-1 day-1 of ganciclovir and 3 x 28 mg kg-1 day-1 of phosphonoacetic acid had no effect on primary SIVern infection in cynomolgus monkeys. These doses of aciclovir, ganciclovir and phosphonoacetic acid are inhibitory to several herpesviruses.The results suggest that the effects of foscarnet and H2G on primary SIVsm infection in monkeys are direct and not mediated through inhibition of a replicating herpesvirus.

Herpesvirus Saimiri Pathogenicity Enhanced by Thymidine Kinase of Herpes Simplex Virus

“…The drugs GCV (Cymeven; Syntex, Grenzach-Wyhlen, Germany) and ACV (Zovirax; Glaxo Wellcome, Hamburg, Germany) were applied subcutaneously at daily doses of 30 mg/kg (ACV) or 15 mg/kg (GCV). The dosage was based on clinical protocols and on previous studies in macaques (Böttiger and Ö berg, 1996). As soon as severe symptoms were realized, the animals were killed and subjected to necropsy.…”