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 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.
Everett
R D
RD
MRC Virology Unit, Church Street, Glasgow G11 5JR, UK. r.everett@vir.gla.ac.uk
Orr
A
A
Preston
C M
CM
D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D018259:Herpesvirus 1, Human / Q000254:growth & development*; D017874:Immediate-Early Proteins / Q000096:biosynthesis*; D007976:Leupeptins / Q000494:pharmacology; D009097:Multienzyme Complexes / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D009687:Nuclear Proteins; D046988:Proteasome Endopeptidase Complex; D020033:Protein Isoforms / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000378:metabolism*; D014775:Virus Activation; D017735:Virus Latency; D014779:Virus Replication / Q000187:drug effects
D015853:Cysteine Proteinase Inhibitors; D017874:Immediate-Early Proteins; D007976:Leupeptins; D009097:Multienzyme Complexes; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D014452:Ubiquitins; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde