A murine model of pseudorabies virus latency

The mouse is a useful laboratory animal for studying various aspects of pseudorabies virus (PRV) virulence. Mice are highly susceptible hosts for PRV infection and are unable to survive acute viral infection. Because of this, mouse models have not been useful for studying PRV latent infections. Here, we report an efficient strategy for establishing latent PRV infections in laboratory mice. Passive transfer of high titered neutralizing antibodies to mice prior to inoculation with highly lethal doses of PRV (Bartha) resulted in survival rates of at least 60% with establishment of latent infections in survivors. Latent PRV infection in mice was demonstrated by: (1) recovery of infectious PRV-Bartha from explants of trigeminal ganglion (TG), and (2) detection of PRV nucleic acids in latently infected TGs by in situ hybridization and polymerase chain reaction (PCR), between 2-8 months post-infection. This PRV latency model indicates that attenuated PRV strains, those currently used extensively in vaccination programs worldwide, can establish a reactivatable latent infection in an experimental host. The mouse model may be particularly useful for examining the molecular bases of PRV latency and reactivation.