A viral activator of gene expression functions via the ubiquitin-proteasome pathway

The ability of herpes simplex virus type 1 (HSV-1) to attain a latent state in sensory neurones and reactivate periodically is crucial for its biologi cal and clinical properties. The active transcription of the entire 152 kb viral genome during lytic replication contrasts with the latent state, whic h is characterized by the production of a single set of nuclear-retained tr anscripts, Reactivation of latent genomes to re-initiate the lytic cycle th erefore involves a profound change in viral transcriptional activity, but t he mechanisms by which this fundamentally important process occurs are yet to be well understood. In this report we show that the stimulation of the o nset of viral lytic infection mediated by the viral immediate-early (IE) pr otein Vmw110 is strikingly inhibited by inactivation of the ubiquitin-prote asome pathway. Similarly, the Vmw110-dependent reactivation of quiescent vi ral genomes in cultured cells is also dependent on proteasome activity, The se results constitute the first demonstration that the transcriptional acti vity of a viral genome can be regulated by protein stability control pathwa ys.