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A viral activator of gene expression functions via the ubiquitin–proteasome pathway
Author(s) -
Everett Roger D.,
Orr Anne,
Preston Chris M.
Publication year - 1998
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/17.24.7161
Subject(s) - lytic cycle , biology , proteasome , viral replication , herpes simplex virus , transcription (linguistics) , microbiology and biotechnology , gene , genome , viral entry , activator (genetics) , viral protein , viral life cycle , virus , viral structural protein , virology , genetics , linguistics , philosophy
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 biological and clinical properties. The active transcription of the entire 152 kb viral genome during lytic replication contrasts with the latent state, which is characterized by the production of a single set of nuclear‐retained transcripts. Reactivation of latent genomes to re‐initiate the lytic cycle therefore involves a profound change in viral transcriptional activity, but the mechanisms by which this fundamentally important process occurs are yet to be well understood. In this report we show that the stimulation of the onset of viral lytic infection mediated by the viral immediate‐early (IE) protein Vmw110 is strikingly inhibited by inactivation of the ubiquitin–proteasome pathway. Similarly, the Vmw110‐dependent reactivation of quiescent viral genomes in cultured cells is also dependent on proteasome activity. These results constitute the first demonstration that the transcriptional activity of a viral genome can be regulated by protein stability control pathways.