IN-VITRO AND IN-VIVO INHIBITION OF MURINE GAMMA-HERPESVIRUS-68 REPLICATION BY SELECTED ANTIVIRAL AGENTS

We have evaluated the susceptibility of the murine gamma herpesvirus 6 8 (MHV-68) to a variety of antiviral agents. The acyclic nucleoside ph osphonate analogs cidofovir [(S)-1-(3-hydroxy-2-phosphonylmethoxypropy l) cytosine], (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)adenine (HPMP A), and adefovir [9-(2-phosphonylmethoxyethyl)adenine] efficiently inh ibited the replication of the virus in Vero cells (50% effective conce ntrations [EC(50)s], 0.008, 0.06, and 2.2 mu g/ml, respectively). Acyc lovir, ganciclovir, and brivudin [(E)-5-(2-bromovinyl)-2'-deoxyuridine ] had equipotent activities (EC(50)s, 1.5 to 8 mu g/ml), whereas fosca rnet and penciclovir were less effective (EC(50)s, 23 and greater than or equal to 30 mu g/ml, respectively). The novel N-7-substituted nucl eoside analog S2242 [7-(1,3-dihydroxy-2-propoxymethyl)purine] inhibite d MHV-68 replication by 50% at 0.2 mu g/ml. The susceptibilities of MH V-68 and Epstein-Barr virus (EBV) to cidofovir, HPMPA, adefovir, and a cyclovir were found to he comparable. However, for penciclovir, gancic lovir, brivudin, and S2242, major differences in the sensitivity of MH V-68 and EBV were observed, suggesting that MHV-68 is not always an op timal surrogate for the study of antiviral strategies for EBV. When ev aluated with a model for lethal MHV-68 infections in mice with severe combined immunodeficiency, cidofovir proved to be very efficient in pr otecting against virus-induced mortality (100% survival at 50 days pos tinfection), whereas acyclovir, brivudin, and adefovir had little or n o effect.