Synergistic antiviral activity of acyclovir and interferon on human cytomegalovirus

Abstract

The efficacy of human alpha interferon (IFN-alpha) combined with 9-(2'-hydroxyethoxymethyl)guanine (acyclovir; ACV), (E)-5-(2-bromovinyl)-2'-deoxyuridine, 9-beta-D-arabinofuranosyladenine, or 1-beta-D-arabinofuranosylcytosine on the inhibition of human cytomegalovirus (HCMV) replication in human embryonic lung cells was analyzed by plaque reduction assays. IFN-alpha combined with 9-beta-D-arabinofuranosyladenine or 1-beta-D-arabinofuranosylcytosine produced an additive antiviral activity with respect to HCMV plaque formation. IFN-alpha combined with (E)-5-(2-bromovinyl)-2'-deoxyuridine also exhibited additive antiviral activity. However, IFN-alpha combined with ACV at concentrations higher than 10 microM consistently yielded synergistic activity in HCMV plaque reduction assays. Kinetic analyses of HCMV replication demonstrated that approximately a 1,000-fold reduction can be attained through the synergistic interaction between ACV (200 microM) and IFN-alpha (42 IU/ml). These data suggest that combined ACV and IFN-alpha treatment may be useful against HCMV infection.