Varicella-zoster virus (VZV) open reading frame 61 protein transactivates VZV gene promoters and enhances the infectivity of VZV DNA.
The varicella-zoster virus (VZV) open reading frame 61 (ORF61) protein is the homolog of herpes simplex virus type 1 (HSV-1) ICP0. Both genes are located in similar parts of the genome, their predicted products share a cysteine-rich motif, and cell lines expressing VZV ORF61 are able to complement an HSV-1 ICP0 deletion mutant (H. Moriuchi, M. Moriuchi, H. A. Smith, S. E. Straus, and J. I. Cohen, J. Virol. 66:7303-7308, 1992). In transient expression assays, HSV-1 ICP0 is a transactivator alone and transactivates in synergy with another viral transactivator, ICP4. However, VZV ORF61 represses the activation by VZV-encoded proteins ORF62 (the homolog of ICP4) and ORF4. To further characterize the function of VZV ORF61 and its role(s) in regulation of viral gene expression, we performed transient expression assays using target promoters from VZV, HSV-1, and unrelated viruses. In the absence of other viral activators, VZV ORF61 transactivated most promoters tested. In addition, a cell line stably expressing VZV ORF61 complemented the HSV-1 mutant in 1814, which lacks the transactivating function of VP16. The cell line expressing VZV ORF61 enhanced the infectivity of HSV-1 virion DNA. Moreover, transient expression of VZV ORF61 also enhanced the infectivity of VZV DNA. These results indicate that VZV ORF61 can stimulate expression of HSV-1 and VZV genes at an early stage in the viral replicative cycle and that ORF61 has an important role in VZV gene regulation.
Medical Virology Section, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
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Moriuchi
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Moriuchi
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Straus
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Cohen
D000818:Animals; D003001:Cloning, Molecular; D015967:Gene Expression Regulation, Viral; D005816:Genetic Complementation Test; D017405:Herpes Simplex Virus Protein Vmw65 / Q000235:genetics; D014645:Herpesvirus 3, Human / Q000235:genetics* / Q000254:growth & development; D006801:Humans; D017874:Immediate-Early Proteins; D066298:In Vitro Techniques; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*; D018139:Simplexvirus / Q000235:genetics* / Q000254:growth & development; D013045:Species Specificity; D015534:Trans-Activators; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics*; D014779:Virus Replication
D017405:Herpes Simplex Virus Protein Vmw65; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D015534:Trans-Activators; D014764:Viral Proteins; C073411:protein 61, Varicella-zoster virus; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1