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Antimicrobial Agents and Chemotherapy, January 1998, p. 170-172, Vol. 42, No. 1
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

In Vitro and In Vivo Inhibition of Murine Gamma Herpesvirus 68 Replication by Selected Antiviral Agents

Johan Neyts* and Erik De Clercq

Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium

Received 27 May 1997/Returned for modification 16 September 1997/Accepted 20 October 1997

We have evaluated the susceptibility of the murine gamma herpesvirus 68 (MHV-68) to a variety of antiviral agents. The acyclic nucleoside phosphonate analogs cidofovir [(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine], (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)adenine (HPMPA), and adefovir [9-(2-phosphonylmethoxyethyl)adenine] efficiently inhibited the replication of the virus in Vero cells (50% effective concentrations [EC50s], 0.008, 0.06, and 2.2 µg/ml, respectively). Acyclovir, ganciclovir, and brivudin [(E)-5-(2-bromovinyl)-2'-deoxyuridine] had equipotent activities (EC50s, 1.5 to 8 µg/ml), whereas foscarnet and penciclovir were less effective (EC50s, 23 and >= 30 µg/ml, respectively). The novel N-7-substituted nucleoside analog S2242 [7-(1,3-dihydroxy-2-propoxymethyl)purine] inhibited MHV-68 replication by 50% at 0.2 µg/ml. The susceptibilities of MHV-68 and Epstein-Barr virus (EBV) to cidofovir, HPMPA, adefovir, and acyclovir were found to be comparable. However, for penciclovir, ganciclovir, brivudin, and S2242, major differences in the sensitivity of MHV-68 and EBV were observed, suggesting that MHV-68 is not always an optimal surrogate for the study of antiviral strategies for EBV. When evaluated with a model for lethal MHV-68 infections in mice with severe combined immunodeficiency, cidofovir proved to be very efficient in protecting against virus-induced mortality (100% survival at 50 days postinfection), whereas acyclovir, brivudin, and adefovir had little or no effect.

* Corresponding author. Mailing address: Rega Institute for Medical Research, K.U. Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium. Phone: 32 16 337353. Fax: 32 16 337340. E-mail: Johan.Neyts{at}rega.kuleuven.ac.be.

Antimicrobial Agents and Chemotherapy, January 1998, p. 170-172, Vol. 42, No. 1
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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