Truncation of the C-terminal acidic transcriptional activation domain of herpes simplex virus VP16 renders expression of the immediate-early genes almost entirely dependent on ICP0.
The herpes simplex virus (HSV) proteins VP16 and ICP0 play key roles in stimulating the onset of the viral lytic cycle. We sought to explore the regulatory links between these proteins by studying the phenotypes of viral mutants in which the activation functions of both were simultaneously inactivated. This analysis unexpectedly revealed that truncation of the C-terminal transcriptional activation domain of VP16 (allele V422) in an ICP0-deficient background almost completely eliminated immediate-early gene expression and virus replication in Vero and HEL cells. The doubly mutant viral genome persisted in a quiescent state for at least 10 days in HEL cells infected at high multiplicity and could be reactivated by superinfection with wild-type HSV. In contrast, the in1814 VP16 mutation produced a markedly less severe phenotype in the same ICP0-deficient background. These data demonstrate that expression of the immediate-early genes requires ICP0 when the C-terminal activation domain of VP16 is deleted and raise the possibility that the in1814 form of VP16 retains a residual ability to stimulate gene expression during virus infection.
Mossman
K L
KL
Department of Medical Microbiology, University of Alberta, Edmonton, Alberta, Canada T6G 2H7.
Smiley
J R
JR
D000818:Animals; D001665:Binding Sites; D002522:Chlorocebus aethiops; D015967:Gene Expression Regulation, Viral; D017405:Herpes Simplex Virus Protein Vmw65 / Q000235:genetics / Q000378:metabolism*; D018259:Herpesvirus 1, Human / Q000235:genetics*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics* / Q000378:metabolism*; D016296:Mutagenesis; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases; D014709:Vero Cells; D010948:Viral Plaque Assay; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins
D017405:Herpes Simplex Virus Protein Vmw65; C057294:ICP22 protein, human herpesvirus 1; C057120:ICP27 protein, human herpesvirus 1; D017874:Immediate-Early Proteins; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C048925:herpes simplex virus, type 1 protein ICP4; C078424:EUS1 protein, Equine herpesvirus 1; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1