Varicella-zoster virus open reading frame 61 protein is functionally homologous to herpes simplex virus type 1 ICP0.
The varicella-zoster virus (VZV) open reading frame 61 (ORF61) protein is thought to be the homolog of herpes simplex virus type 1 (HSV-1) ICP0, based on gene location and limited amino acid homology. However, HSV-1 ICP0 trans activates HSV-1 genes, while VZV ORF61 protein trans represses the function of VZV trans activators on VZV promoters in transient expression assays. To investigate the functional relatedness of HSV-1 ICP0 and VZV ORF61 protein, we established Vero and MeWo cell lines which stably express VZV ORF61 under the control of a metallothionein promoter and performed complementation studies with an HSV-1 ICP0 deletion mutant (7134). Mutant 7134 is impaired for plaque formation and replication at a low multiplicity of infection in cell culture, but these defects were complemented by up to 200-fold in Vero cell lines expressing VZV ORF61. Likewise, the efficiency of plaque formation was improved by up to 100-fold in MeWo cell lines expressing VZV ORF61. A cell line expressing another VZV immediate-early gene product (ORF62) was unable to complement mutant 7134. HSV-1 mutants which are deleted for other HSV-1 immediate-early gene products (ICP4, ICP27) were unable to grow in VZV ORF61-expressing cell lines. These results indicate that, despite marked differences in their sequences and in effects on their cognate promoters in transient expression assays, VZV ORF61 protein is the functional homolog of HSV-1 ICP0.
Medical Virology Section, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
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Moriuchi
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Moriuchi
H A
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Smith
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Straus
J I
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Cohen
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D002352:Carrier Proteins / Q000378:metabolism*; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D002522:Chlorocebus aethiops; D005814:Genes, Viral; D005816:Genetic Complementation Test; D014645:Herpesvirus 3, Human / Q000235:genetics* / Q000502:physiology; D006801:Humans; D017874:Immediate-Early Proteins; D008545:Melanoma; D008668:Metallothionein / Q000235:genetics; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D016366:Open Reading Frames; D010957:Plasmids; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D018139:Simplexvirus / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases; D014709:Vero Cells; D010948:Viral Plaque Assay; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication
D002352:Carrier Proteins; D017874:Immediate-Early Proteins; D009838:Oligodeoxyribonucleotides; D012097:Repressor Proteins; D014764:Viral Proteins; C073411:protein 61, Varicella-zoster virus; D008668:Metallothionein; D015500:Chloramphenicol O-Acetyltransferase; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1