Varicella-zoster virus open reading frame 10 protein, the herpes simplex virus VP16 homolog, transactivates herpesvirus immediate-early gene promoters.
The varicella-zoster virus (VZV) open reading frame 10 (ORF10) protein is the homolog of the herpes simplex virus type 1 (HSV-1) protein VP16. These are two virion tegument proteins that have extensive amino acid sequence identity in their amino-terminal and middle domains. ORF10, however, lacks the acidic carboxy terminus which is critical for transactivation by VP16. Earlier studies showed that VZV ORF10 does not form a tertiary complex with the TAATGARAT regulatory element (where R is a purine) with which HSV-1 VP16 interacts, suggesting that ORF10 may not have transactivating ability. Using transient-expression assays, we show that VZV ORF10 is able to transactivate VZV immediate-early (IE) gene (ORF62) and HSV-1 IE gene (ICP4 and ICP0) promoters. Furthermore, cell lines stably expressing ORF10 complement the HSV-1 mutant in1814, which lacks the transactivating function of VP16, and enhance the de novo synthesis of infectious virus following transfection of HSV-1 virion DNA. These results indicate that ORF10, like its HSV-1 homolog VP16, is a transactivating protein despite the absence of sequences similar to the VP16 carboxy-terminal domain. The transactivating function of the VZV ORF10 tegument protein may be critical for efficient initiation of viral infection.
Moriuchi
H
H
Medical Virology Section, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
Moriuchi
M
M
Straus
S E
SE
Cohen
J I
JI
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D005816:Genetic Complementation Test; D014645:Herpesvirus 3, Human / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D006801:Humans; D017874:Immediate-Early Proteins; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D018139:Simplexvirus / Q000235:genetics; D015533:Transcriptional Activation; D014162:Transfection; D014170:Transformation, Genetic; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics*; D014774:Virulence; D014779:Virus Replication
D004279:DNA, Viral; D004268:DNA-Binding Proteins; C045462:ICP8 protein, Simplexvirus; C050678:IE1 protein, Human herpesvirus 1; D017874:Immediate-Early Proteins; D014764:Viral Proteins