2′-Deoxy-5-Ethyl-β-4′-Thiouridine Inhibits Replication of Murine Gammaherpesvirus and Delays the Onset of Virus Latency

Abstract

The antiviral thionucleoside analogue 2′-deoxy-5-ethyl-β-4′-thiouridine (4′-S-EtdU) was shown to be a more potent inhibitor of gammaherpesvirus infection than acyclovir. This compound inhibits replication of murine herpesvirus (MHV)-68 in the lungs of mice when given 3 days post-infection. However, as with other nucleoside analogues, it was unable to prevent the establishment of latency, despite delaying the onset of latent infection in the spleen. In contrast, virus persistence in the lung was inhibited following drug treatment, although persistence was re-established in mice when treatment was suspended after 12 days. These data suggest that 4′-S-EtdU is a highly effective inhibitor of murine gammaherpesvirus replication and as such provides a powerful tool to study the pathogenesis of this virus in vivo.