Abstract
Accumulating evidence indicates that the product of the putative immediate-early gene ORF62 (IE62) activates varicella-zoster virus (VZV) genes thought to represent all three kinetic classes, namely, immediate-early (alpha), early (beta), and late (gamma) classes, of VZV genes as well as a variety heterologous gene promoters. However, the mechanism(s) by which IE62 protein mediates transactivation of these diverse VZV and heterologous gene promoters remains to be elucidated. In this study, by using yeast GAL4 protein chimeras, the coding regions of VZV ORF62 possessing activation domains have been assessed. We demonstrate that the VZV IE62 protein contains a potent activation domain in the N-terminal portion of the molecule, encoded within the first 86 codons of ORF62. The predicted secondary structure profile and the acid-base composition of this IE62 domain resemble those of other transregulatory proteins whose activation is mediated through acidic, hydrophobic elements. In addition, we show that deletion of this activation domain from the 1,310-residue native IE62 protein results in ablation of the transactivator function of IE62. We also present evidence that the mutant IE62 protein lacking the activation domain, though devoid of transactivation ability, was still capable of interfering with the activation of target promoters by the native, full-length IE62.
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- Alwine J. C., Steinhart W. L., Hill C. W. Transcription of herpes simplex type 1 DNA in nuclei isolated from infected HEp-2 and KB cells. Virology. 1974 Jul;60(1):302–307. doi: 10.1016/0042-6822(74)90390-0. [DOI] [PubMed] [Google Scholar]
- Batterson W., Roizman B. Characterization of the herpes simplex virion-associated factor responsible for the induction of alpha genes. J Virol. 1983 May;46(2):371–377. doi: 10.1128/jvi.46.2.371-377.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berger S. L., Cress W. D., Cress A., Triezenberg S. J., Guarente L. Selective inhibition of activated but not basal transcription by the acidic activation domain of VP16: evidence for transcriptional adaptors. Cell. 1990 Jun 29;61(7):1199–1208. doi: 10.1016/0092-8674(90)90684-7. [DOI] [PubMed] [Google Scholar]
- Campbell M. E., Palfreyman J. W., Preston C. M. Identification of herpes simplex virus DNA sequences which encode a trans-acting polypeptide responsible for stimulation of immediate early transcription. J Mol Biol. 1984 Nov 25;180(1):1–19. doi: 10.1016/0022-2836(84)90427-3. [DOI] [PubMed] [Google Scholar]
- Carey M., Leatherwood J., Ptashne M. A potent GAL4 derivative activates transcription at a distance in vitro. Science. 1990 Feb 9;247(4943):710–712. doi: 10.1126/science.2405489. [DOI] [PubMed] [Google Scholar]
- Cheung A. K. DNA nucleotide sequence analysis of the immediate-early gene of pseudorabies virus. Nucleic Acids Res. 1989 Jun 26;17(12):4637–4646. doi: 10.1093/nar/17.12.4637. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clements J. B., Watson R. J., Wilkie N. M. Temporal regulation of herpes simplex virus type 1 transcription: location of transcripts on the viral genome. Cell. 1977 Sep;12(1):275–285. doi: 10.1016/0092-8674(77)90205-7. [DOI] [PubMed] [Google Scholar]
- Costanzo F., Campadelli-Fiume G., Foa-Tomasi L., Cassai E. Evidence that herpes simplex virus DNA is transcribed by cellular RNA polymerase B. J Virol. 1977 Mar;21(3):996–1001. doi: 10.1128/jvi.21.3.996-1001.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Davison A. J., Scott J. E. The complete DNA sequence of varicella-zoster virus. J Gen Virol. 1986 Sep;67(Pt 9):1759–1816. doi: 10.1099/0022-1317-67-9-1759. [DOI] [PubMed] [Google Scholar]
- DeLuca N. A., McCarthy A. M., Schaffer P. A. Isolation and characterization of deletion mutants of herpes simplex virus type 1 in the gene encoding immediate-early regulatory protein ICP4. J Virol. 1985 Nov;56(2):558–570. doi: 10.1128/jvi.56.2.558-570.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DeLuca N. A., Schaffer P. A. Activities of herpes simplex virus type 1 (HSV-1) ICP4 genes specifying nonsense peptides. Nucleic Acids Res. 1987 Jun 11;15(11):4491–4511. doi: 10.1093/nar/15.11.4491. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Disney G. H., Everett R. D. A herpes simplex virus type 1 recombinant with both copies of the Vmw175 coding sequences replaced by the homologous varicella-zoster virus open reading frame. J Gen Virol. 1990 Nov;71(Pt 11):2681–2689. doi: 10.1099/0022-1317-71-11-2681. [DOI] [PubMed] [Google Scholar]
- Dixon R. A., Schaffer P. A. Fine-structure mapping and functional analysis of temperature-sensitive mutants in the gene encoding the herpes simplex virus type 1 immediate early protein VP175. J Virol. 1980 Oct;36(1):189–203. doi: 10.1128/jvi.36.1.189-203.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Felser J. M., Kinchington P. R., Inchauspe G., Straus S. E., Ostrove J. M. Cell lines containing varicella-zoster virus open reading frame 62 and expressing the "IE" 175 protein complement ICP4 mutants of herpes simplex virus type 1. J Virol. 1988 Jun;62(6):2076–2082. doi: 10.1128/jvi.62.6.2076-2082.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Felser J. M., Straus S. E., Ostrove J. M. Varicella-zoster virus complements herpes simplex virus type 1 temperature-sensitive mutants. J Virol. 1987 Jan;61(1):225–228. doi: 10.1128/jvi.61.1.225-228.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Folks T., Benn S., Rabson A., Theodore T., Hoggan M. D., Martin M., Lightfoote M., Sell K. Characterization of a continuous T-cell line susceptible to the cytopathic effects of the acquired immunodeficiency syndrome (AIDS)-associated retrovirus. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4539–4543. doi: 10.1073/pnas.82.13.4539. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Giniger E., Varnum S. M., Ptashne M. Specific DNA binding of GAL4, a positive regulatory protein of yeast. Cell. 1985 Apr;40(4):767–774. doi: 10.1016/0092-8674(85)90336-8. [DOI] [PubMed] [Google Scholar]
- Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Grundy F. J., Baumann R. P., O'Callaghan D. J. DNA sequence and comparative analyses of the equine herpesvirus type 1 immediate early gene. Virology. 1989 Sep;172(1):223–236. doi: 10.1016/0042-6822(89)90124-4. [DOI] [PubMed] [Google Scholar]
- Han M., Grunstein M. Nucleosome loss activates yeast downstream promoters in vivo. Cell. 1988 Dec 23;55(6):1137–1145. doi: 10.1016/0092-8674(88)90258-9. [DOI] [PubMed] [Google Scholar]
- Holland L. E., Anderson K. P., Stringer J. R., Wagner E. K. Isolation and localization of herpes simplex virus type 1 mRNA abundant before viral DNA synthesis. J Virol. 1979 Aug;31(2):447–462. doi: 10.1128/jvi.31.2.447-462.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Honess R. W., Roizman B. Regulation of herpesvirus macromolecular synthesis. I. Cascade regulation of the synthesis of three groups of viral proteins. J Virol. 1974 Jul;14(1):8–19. doi: 10.1128/jvi.14.1.8-19.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Honess R. W., Roizman B. Regulation of herpesvirus macromolecular synthesis: sequential transition of polypeptide synthesis requires functional viral polypeptides. Proc Natl Acad Sci U S A. 1975 Apr;72(4):1276–1280. doi: 10.1073/pnas.72.4.1276. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Inchauspe G., Nagpal S., Ostrove J. M. Mapping of two varicella-zoster virus-encoded genes that activate the expression of viral early and late genes. Virology. 1989 Dec;173(2):700–709. doi: 10.1016/0042-6822(89)90583-7. [DOI] [PubMed] [Google Scholar]
- Johnson P. F., McKnight S. L. Eukaryotic transcriptional regulatory proteins. Annu Rev Biochem. 1989;58:799–839. doi: 10.1146/annurev.bi.58.070189.004055. [DOI] [PubMed] [Google Scholar]
- Johnston M. A model fungal gene regulatory mechanism: the GAL genes of Saccharomyces cerevisiae. Microbiol Rev. 1987 Dec;51(4):458–476. doi: 10.1128/mr.51.4.458-476.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kelleher R. J., 3rd, Flanagan P. M., Kornberg R. D. A novel mediator between activator proteins and the RNA polymerase II transcription apparatus. Cell. 1990 Jun 29;61(7):1209–1215. doi: 10.1016/0092-8674(90)90685-8. [DOI] [PubMed] [Google Scholar]
- Kinchington P. R., Hougland J. K., Arvin A. M., Ruyechan W. T., Hay J. The varicella-zoster virus immediate-early protein IE62 is a major component of virus particles. J Virol. 1992 Jan;66(1):359–366. doi: 10.1128/jvi.66.1.359-366.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kristie T. M., Roizman B. Separation of sequences defining basal expression from those conferring alpha gene recognition within the regulatory domains of herpes simplex virus 1 alpha genes. Proc Natl Acad Sci U S A. 1984 Jul;81(13):4065–4069. doi: 10.1073/pnas.81.13.4065. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lillie J. W., Green M. R. Transcription activation by the adenovirus E1a protein. Nature. 1989 Mar 2;338(6210):39–44. doi: 10.1038/338039a0. [DOI] [PubMed] [Google Scholar]
- Lin Y. S., Carey M. F., Ptashne M., Green M. R. GAL4 derivatives function alone and synergistically with mammalian activators in vitro. Cell. 1988 Aug 26;54(5):659–664. doi: 10.1016/s0092-8674(88)80010-2. [DOI] [PubMed] [Google Scholar]
- Mackem S., Roizman B. Structural features of the herpes simplex virus alpha gene 4, 0, and 27 promoter-regulatory sequences which confer alpha regulation on chimeric thymidine kinase genes. J Virol. 1982 Dec;44(3):939–949. doi: 10.1128/jvi.44.3.939-949.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McGeoch D. J., Dalrymple M. A., Davison A. J., Dolan A., Frame M. C., McNab D., Perry L. J., Scott J. E., Taylor P. The complete DNA sequence of the long unique region in the genome of herpes simplex virus type 1. J Gen Virol. 1988 Jul;69(Pt 7):1531–1574. doi: 10.1099/0022-1317-69-7-1531. [DOI] [PubMed] [Google Scholar]
- McGeoch D. J., Dolan A., Donald S., Brauer D. H. Complete DNA sequence of the short repeat region in the genome of herpes simplex virus type 1. Nucleic Acids Res. 1986 Feb 25;14(4):1727–1745. doi: 10.1093/nar/14.4.1727. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mitchell P. J., Tjian R. Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins. Science. 1989 Jul 28;245(4916):371–378. doi: 10.1126/science.2667136. [DOI] [PubMed] [Google Scholar]
- Mosca J. D., Pitha P. M., Hayward G. S. Herpes simplex virus infection selectively stimulates accumulation of beta interferon reporter gene mRNA by a posttranscriptional mechanism. J Virol. 1992 Jun;66(6):3811–3822. doi: 10.1128/jvi.66.6.3811-3822.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- O'Hare P., Hayward G. S. Three trans-acting regulatory proteins of herpes simplex virus modulate immediate-early gene expression in a pathway involving positive and negative feedback regulation. J Virol. 1985 Dec;56(3):723–733. doi: 10.1128/jvi.56.3.723-733.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- PUCK T. T., CIECIURA S. J., ROBINSON A. Genetics of somatic mammalian cells. III. Long-term cultivation of euploid cells from human and animal subjects. J Exp Med. 1958 Dec 1;108(6):945–956. doi: 10.1084/jem.108.6.945. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pellett P. E., McKnight J. L., Jenkins F. J., Roizman B. Nucleotide sequence and predicted amino acid sequence of a protein encoded in a small herpes simplex virus DNA fragment capable of trans-inducing alpha genes. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5870–5874. doi: 10.1073/pnas.82.17.5870. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Perera L. P., Mosca J. D., Ruyechan W. T., Hay J. Regulation of varicella-zoster virus gene expression in human T lymphocytes. J Virol. 1992 Sep;66(9):5298–5304. doi: 10.1128/jvi.66.9.5298-5304.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Perera L. P., Mosca J. D., Sadeghi-Zadeh M., Ruyechan W. T., Hay J. The varicella-zoster virus immediate early protein, IE62, can positively regulate its cognate promoter. Virology. 1992 Nov;191(1):346–354. doi: 10.1016/0042-6822(92)90197-w. [DOI] [PubMed] [Google Scholar]
- Perera L. P., Samuel J. E., Holmes R. K., O'Brien A. D. Identification of three amino acid residues in the B subunit of Shiga toxin and Shiga-like toxin type II that are essential for holotoxin activity. J Bacteriol. 1991 Feb;173(3):1151–1160. doi: 10.1128/jb.173.3.1151-1160.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pizzorno M. C., Mullen M. A., Chang Y. N., Hayward G. S. The functionally active IE2 immediate-early regulatory protein of human cytomegalovirus is an 80-kilodalton polypeptide that contains two distinct activator domains and a duplicated nuclear localization signal. J Virol. 1991 Jul;65(7):3839–3852. doi: 10.1128/jvi.65.7.3839-3852.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Preston C. M. Abnormal properties of an immediate early polypeptide in cells infected with the herpes simplex virus type 1 mutant tsK. J Virol. 1979 Nov;32(2):357–369. doi: 10.1128/jvi.32.2.357-369.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Preston C. M. Control of herpes simplex virus type 1 mRNA synthesis in cells infected with wild-type virus or the temperature-sensitive mutant tsK. J Virol. 1979 Jan;29(1):275–284. doi: 10.1128/jvi.29.1.275-284.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ptashne M. Gene regulation by proteins acting nearby and at a distance. Nature. 1986 Aug 21;322(6081):697–701. doi: 10.1038/322697a0. [DOI] [PubMed] [Google Scholar]
- Ptashne M. How eukaryotic transcriptional activators work. Nature. 1988 Oct 20;335(6192):683–689. doi: 10.1038/335683a0. [DOI] [PubMed] [Google Scholar]
- Sadowski I., Ma J., Triezenberg S., Ptashne M. GAL4-VP16 is an unusually potent transcriptional activator. Nature. 1988 Oct 6;335(6190):563–564. doi: 10.1038/335563a0. [DOI] [PubMed] [Google Scholar]
- Sadowski I., Ptashne M. A vector for expressing GAL4(1-147) fusions in mammalian cells. Nucleic Acids Res. 1989 Sep 25;17(18):7539–7539. doi: 10.1093/nar/17.18.7539. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shiraki K., Hyman R. W. The immediate early proteins of varicella-zoster virus. Virology. 1987 Feb;156(2):423–426. doi: 10.1016/0042-6822(87)90423-5. [DOI] [PubMed] [Google Scholar]
- Telford E. A., Watson M. S., McBride K., Davison A. J. The DNA sequence of equine herpesvirus-1. Virology. 1992 Jul;189(1):304–316. doi: 10.1016/0042-6822(92)90706-u. [DOI] [PubMed] [Google Scholar]
- Watson R. J., Clements J. B. A herpes simplex virus type 1 function continuously required for early and late virus RNA synthesis. Nature. 1980 May 29;285(5763):329–330. doi: 10.1038/285329a0. [DOI] [PubMed] [Google Scholar]
- Wu C. L., Wilcox K. W. The conserved DNA-binding domains encoded by the herpes simplex virus type 1 ICP4, pseudorabies virus IE180, and varicella-zoster virus ORF62 genes recognize similar sites in the corresponding promoters. J Virol. 1991 Mar;65(3):1149–1159. doi: 10.1128/jvi.65.3.1149-1159.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]