title: Varicella-zoster virus open reading frame 4 protein is functionally distinct from and does not complement its herpes simplex virus type 1 homolog, ICP27.
abstract: Varicella-zoster virus (VZV) open reading frame 4 (ORF4) encodes a putative immediate-early protein which is homologous to herpes simplex virus type 1 (HSV-1) ICP27 on the basis of gene location and similarity in amino acid sequence. In transient expression assays, however, ORF4 and ICP27 exhibit different properties. ICP27 alone has little activity on target plasmids, but it acts as a transactivator or a transrepressor in the presence of other HSV-1 transactivators. In contrast, ORF4 directly transactivates plasmids containing homologous or heterologous promoters and has no apparent transrepressing activity. To further illuminate the functional similarities and differences between ORF4 and ICP27, Vero cell lines which express ORF4 under the inducible metallothionein promoter were constructed. Cell lines expressing functionally active ORF4 protein upregulated the expression of transfected VZV target plasmids but were unable to efficiently complement HSV-1 ICP27 mutants. These results indicate that, despite structural similarities, VZV ORF4 and HSV-1 ICP27 behave differently in transient expression assays and may play different roles in virus replication.
authors.affiliation: Medical Virology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: H
authors.initials: H
authors.lastname: Moriuchi
authors.forename: M
authors.initials: M
authors.lastname: Moriuchi
authors.forename: H A
authors.initials: HA
authors.lastname: Smith
authors.forename: J I
authors.initials: JI
authors.lastname: Cohen
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D005816:Genetic Complementation Test; D014645:Herpesvirus 3, Human / Q000235:genetics*; D017874:Immediate-Early Proteins / Q000096:biosynthesis / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D018139:Simplexvirus / Q000235:genetics* / Q000254:growth & development; D015534:Trans-Activators / Q000235:genetics; D015533:Transcriptional Activation; D014162:Transfection; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000235:genetics; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics*; D014779:Virus Replication
chemical_list: C057120:ICP27 protein, human herpesvirus 1; C074221:IE62 protein, Human herpesvirus 3; D017874:Immediate-Early Proteins; C085824:ORF4 protein, Human herpesvirus 3; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014759:Viral Envelope Proteins; D014764:Viral Proteins