Protection against wild-type murine gammaherpesvirus-68 latency by a latency-deficient mutant

A murine gammaherpesvirus-68 (MHV-68) mutant with deregulated transcription of its ORF50 transactivator was severely impaired in latency establishment. The deregulated virus showed reduced immunogenicity, probably reflecting a lower antigen load. However, it still elicited effective immunity to a subsequent wild-type (WT) virus challenge. Infection was not completely prevented, but was very substantially reduced in extent and the long-term level of WT viral DNA in lungs and spleens remained low. Thus latency-deficient MHV-68 illustrates a possible general approach to creating attenuated gammaherpesvirus vaccines that can protect against pathogenic WT infections.