Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1997 Mar;71(3):1784–1793. doi: 10.1128/jvi.71.3.1784-1793.1997

Herpes simplex virus immediate-early proteins ICP0 and ICP4 activate the endogenous human alpha-globin gene in nonerythroid cells.

P Cheung 1, B Panning 1, J R Smiley 1
PMCID: PMC191247  PMID: 9032307

Abstract

Globin genes are normally expressed only in erythroid cell lineages. However, we found that the endogenous alpha-globin gene is activated following infection of human fibroblasts and HeLa cells with herpes simplex virus (HSV), leading to accumulation of correctly initiated transcripts driven by the alpha-globin promoter. The alpha1- and alpha2-globin genes were both induced, but expression of beta- or zeta-globin genes could not be detected. Experiments using HSV mutants showed that null mutations in the genes encoding the viral immediate-early proteins ICP4 and ICP22 reduced induction approximately 10-fold, while loss of ICP0 function had a smaller inhibitory effect. Transient transfection experiments showed that ICP0 and ICP4 are each sufficient to trigger detectable expression of the endogenous gene, while ICP22 had no detectable effect in this assay. ICP4 also strongly enhanced expression of transfected copies of the alpha2-globin gene. In contrast, the adenovirus E1a protein did not activate the endogenous gene and inhibited expression of the plasmid-borne alpha2-globin gene. Previous studies have led to the hypothesis that chromosomal alpha-globin genes are subject to chromatin-dependent repression mechanism that prevents expression in nonerythroid cells. Our data suggest that HSV ICP0 and ICP4 either break or bypass this cellular gene silencing mechanism.

Full Text

The Full Text of this article is available as a PDF (1.1 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Antequera F., Boyes J., Bird A. High levels of de novo methylation and altered chromatin structure at CpG islands in cell lines. Cell. 1990 Aug 10;62(3):503–514. doi: 10.1016/0092-8674(90)90015-7. [DOI] [PubMed] [Google Scholar]
  2. Antequera F., Macleod D., Bird A. P. Specific protection of methylated CpGs in mammalian nuclei. Cell. 1989 Aug 11;58(3):509–517. doi: 10.1016/0092-8674(89)90431-5. [DOI] [PubMed] [Google Scholar]
  3. Baron M. H., Maniatis T. Rapid reprogramming of globin gene expression in transient heterokaryons. Cell. 1986 Aug 15;46(4):591–602. doi: 10.1016/0092-8674(86)90885-8. [DOI] [PubMed] [Google Scholar]
  4. Baron M. H., Maniatis T. Regulated expression of human alpha- and beta-globin genes in transient heterokaryons. Mol Cell Biol. 1991 Mar;11(3):1239–1247. doi: 10.1128/mcb.11.3.1239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Bautista D. S., Hitt M., McGrory J., Graham F. L. Isolation and characterization of insertion mutants in E1A of adenovirus type 5. Virology. 1991 Jun;182(2):578–596. doi: 10.1016/0042-6822(91)90599-7. [DOI] [PubMed] [Google Scholar]
  7. Bentley D. L. Regulation of transcriptional elongation by RNA polymerase II. Curr Opin Genet Dev. 1995 Apr;5(2):210–216. doi: 10.1016/0959-437x(95)80010-7. [DOI] [PubMed] [Google Scholar]
  8. Berk A. J. Adenovirus promoters and E1A transactivation. Annu Rev Genet. 1986;20:45–79. doi: 10.1146/annurev.ge.20.120186.000401. [DOI] [PubMed] [Google Scholar]
  9. Bickmore W. A., Sumner A. T. Mammalian chromosome banding--an expression of genome organization. Trends Genet. 1989 May;5(5):144–148. doi: 10.1016/0168-9525(89)90055-3. [DOI] [PubMed] [Google Scholar]
  10. Bird A. P., Taggart M. H., Nicholls R. D., Higgs D. R. Non-methylated CpG-rich islands at the human alpha-globin locus: implications for evolution of the alpha-globin pseudogene. EMBO J. 1987 Apr;6(4):999–1004. doi: 10.1002/j.1460-2075.1987.tb04851.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Brickner H. E., Zhu X. X., Atweh G. F. A novel regulatory element of the human alpha-globin gene responsible for its constitutive expression. J Biol Chem. 1991 Aug 15;266(23):15363–15368. [PubMed] [Google Scholar]
  12. Cai W. Z., Schaffer P. A. Herpes simplex virus type 1 ICP0 plays a critical role in the de novo synthesis of infectious virus following transfection of viral DNA. J Virol. 1989 Nov;63(11):4579–4589. doi: 10.1128/jvi.63.11.4579-4589.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Cai W., Schaffer P. A. Herpes simplex virus type 1 ICP0 regulates expression of immediate-early, early, and late genes in productively infected cells. J Virol. 1992 May;66(5):2904–2915. doi: 10.1128/jvi.66.5.2904-2915.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Carrozza M. J., DeLuca N. A. Interaction of the viral activator protein ICP4 with TFIID through TAF250. Mol Cell Biol. 1996 Jun;16(6):3085–3093. doi: 10.1128/mcb.16.6.3085. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Charnay P., Treisman R., Mellon P., Chao M., Axel R., Maniatis T. Differences in human alpha- and beta-globin gene expression in mouse erythroleukemia cells: the role of intragenic sequences. Cell. 1984 Aug;38(1):251–263. doi: 10.1016/0092-8674(84)90547-6. [DOI] [PubMed] [Google Scholar]
  17. Coen D. M., Weinheimer S. P., McKnight S. L. A genetic approach to promoter recognition during trans induction of viral gene expression. Science. 1986 Oct 3;234(4772):53–59. doi: 10.1126/science.3018926. [DOI] [PubMed] [Google Scholar]
  18. Craddock C. F., Vyas P., Sharpe J. A., Ayyub H., Wood W. G., Higgs D. R. Contrasting effects of alpha and beta globin regulatory elements on chromatin structure may be related to their different chromosomal environments. EMBO J. 1995 Apr 18;14(8):1718–1726. doi: 10.1002/j.1460-2075.1995.tb07161.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Davison M. J., Preston V. G., McGeoch D. J. Determination of the sequence alteration in the DNA of the herpes simplex virus type 1 temperature-sensitive mutant ts K. J Gen Virol. 1984 May;65(Pt 5):859–863. doi: 10.1099/0022-1317-65-5-859. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. 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]
  22. DeLuca N. A., Schaffer P. A. Physical and functional domains of the herpes simplex virus transcriptional regulatory protein ICP4. J Virol. 1988 Mar;62(3):732–743. doi: 10.1128/jvi.62.3.732-743.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Desai P., Ramakrishnan R., Lin Z. W., Osak B., Glorioso J. C., Levine M. The RR1 gene of herpes simplex virus type 1 is uniquely trans activated by ICP0 during infection. J Virol. 1993 Oct;67(10):6125–6135. doi: 10.1128/jvi.67.10.6125-6135.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Everett R. D. A detailed analysis of an HSV-1 early promoter: sequences involved in trans-activation by viral immediate-early gene products are not early-gene specific. Nucleic Acids Res. 1984 Apr 11;12(7):3037–3056. doi: 10.1093/nar/12.7.3037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Everett R. D. Activation of cellular promoters during herpes virus infection of biochemically transformed cells. EMBO J. 1985 Aug;4(8):1973–1980. doi: 10.1002/j.1460-2075.1985.tb03880.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Everett R. D. DNA sequence elements required for regulated expression of the HSV-1 glycoprotein D gene lie within 83 bp of the RNA capsites. Nucleic Acids Res. 1983 Oct 11;11(19):6647–6666. doi: 10.1093/nar/11.19.6647. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Everett R. D. Promoter sequence and cell type can dramatically affect the efficiency of transcriptional activation induced by herpes simplex virus type 1 and its immediate-early gene products Vmw175 and Vmw110. J Mol Biol. 1988 Oct 5;203(3):739–751. doi: 10.1016/0022-2836(88)90206-9. [DOI] [PubMed] [Google Scholar]
  28. Everett R. D. The regulation of transcription of viral and cellular genes by herpesvirus immediate-early gene products (review). Anticancer Res. 1987 Jul-Aug;7(4A):589–604. [PubMed] [Google Scholar]
  29. Faber S. W., Wilcox K. W. Association of herpes simplex virus regulatory protein ICP4 with sequences spanning the ICP4 gene transcription initiation site. Nucleic Acids Res. 1988 Jan 25;16(2):555–570. doi: 10.1093/nar/16.2.555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Faber S. W., Wilcox K. W. Association of the herpes simplex virus regulatory protein ICP4 with specific nucleotide sequences in DNA. Nucleic Acids Res. 1986 Aug 11;14(15):6067–6083. doi: 10.1093/nar/14.15.6067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Forrester W. C., Epner E., Driscoll M. C., Enver T., Brice M., Papayannopoulou T., Groudine M. A deletion of the human beta-globin locus activation region causes a major alteration in chromatin structure and replication across the entire beta-globin locus. Genes Dev. 1990 Oct;4(10):1637–1649. doi: 10.1101/gad.4.10.1637. [DOI] [PubMed] [Google Scholar]
  32. Forrester W. C., Takegawa S., Papayannopoulou T., Stamatoyannopoulos G., Groudine M. Evidence for a locus activation region: the formation of developmentally stable hypersensitive sites in globin-expressing hybrids. Nucleic Acids Res. 1987 Dec 23;15(24):10159–10177. doi: 10.1093/nar/15.24.10159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Goldstein D. J., Weller S. K. Herpes simplex virus type 1-induced ribonucleotide reductase activity is dispensable for virus growth and DNA synthesis: isolation and characterization of an ICP6 lacZ insertion mutant. J Virol. 1988 Jan;62(1):196–205. doi: 10.1128/jvi.62.1.196-205.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Graham F. L., Smiley J., Russell W. C., Nairn R. Characteristics of a human cell line transformed by DNA from human adenovirus type 5. J Gen Virol. 1977 Jul;36(1):59–74. doi: 10.1099/0022-1317-36-1-59. [DOI] [PubMed] [Google Scholar]
  35. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  36. Green M. R., Treisman R., Maniatis T. Transcriptional activation of cloned human beta-globin genes by viral immediate-early gene products. Cell. 1983 Nov;35(1):137–148. doi: 10.1016/0092-8674(83)90216-7. [DOI] [PubMed] [Google Scholar]
  37. Grosveld F., Dillon N., Higgs D. The regulation of human globin gene expression. Baillieres Clin Haematol. 1993 Mar;6(1):31–55. doi: 10.1016/s0950-3536(05)80065-4. [DOI] [PubMed] [Google Scholar]
  38. Grosveld F., van Assendelft G. B., Greaves D. R., Kollias G. Position-independent, high-level expression of the human beta-globin gene in transgenic mice. Cell. 1987 Dec 24;51(6):975–985. doi: 10.1016/0092-8674(87)90584-8. [DOI] [PubMed] [Google Scholar]
  39. Groudine M., Kohwi-Shigematsu T., Gelinas R., Stamatoyannopoulos G., Papayannopoulou T. Human fetal to adult hemoglobin switching: changes in chromatin structure of the beta-globin gene locus. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7551–7555. doi: 10.1073/pnas.80.24.7551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Gu B., DeLuca N. Requirements for activation of the herpes simplex virus glycoprotein C promoter in vitro by the viral regulatory protein ICP4. J Virol. 1994 Dec;68(12):7953–7965. doi: 10.1128/jvi.68.12.7953-7965.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Hall J. D., Coen D. M., Fisher B. L., Weisslitz M., Randall S., Almy R. E., Gelep P. T., Schaffer P. A. Generation of genetic diversity in herpes simplex virus: an antimutator phenotype maps to the DNA polymerase locus. Virology. 1984 Jan 15;132(1):26–37. doi: 10.1016/0042-6822(84)90088-6. [DOI] [PubMed] [Google Scholar]
  42. Harris R. A., Everett R. D., Zhu X. X., Silverstein S., Preston C. M. Herpes simplex virus type 1 immediate-early protein Vmw110 reactivates latent herpes simplex virus type 2 in an in vitro latency system. J Virol. 1989 Aug;63(8):3513–3515. doi: 10.1128/jvi.63.8.3513-3515.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Higgs D. R., Wood W. G., Jarman A. P., Sharpe J., Lida J., Pretorius I. M., Ayyub H. A major positive regulatory region located far upstream of the human alpha-globin gene locus. Genes Dev. 1990 Sep;4(9):1588–1601. doi: 10.1101/gad.4.9.1588. [DOI] [PubMed] [Google Scholar]
  44. Holmquist G. P. Role of replication time in the control of tissue-specific gene expression. Am J Hum Genet. 1987 Feb;40(2):151–173. [PMC free article] [PubMed] [Google Scholar]
  45. Homa F. L., Glorioso J. C., Levine M. A specific 15-bp TATA box promoter element is required for expression of a herpes simplex virus type 1 late gene. Genes Dev. 1988 Jan;2(1):40–53. doi: 10.1101/gad.2.1.40. [DOI] [PubMed] [Google Scholar]
  46. Humphries R. K., Ley T., Turner P., Moulton A. D., Nienhuis A. W. Differences in human alpha-, beta- and delta-globin gene expression in monkey kidney cells. Cell. 1982 Aug;30(1):173–183. doi: 10.1016/0092-8674(82)90023-x. [DOI] [PubMed] [Google Scholar]
  47. Imbalzano A. N., Coen D. M., DeLuca N. A. Herpes simplex virus transactivator ICP4 operationally substitutes for the cellular transcription factor Sp1 for efficient expression of the viral thymidine kinase gene. J Virol. 1991 Feb;65(2):565–574. doi: 10.1128/jvi.65.2.565-574.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Imbalzano A. N., DeLuca N. A. Substitution of a TATA box from a herpes simplex virus late gene in the viral thymidine kinase promoter alters ICP4 inducibility but not temporal expression. J Virol. 1992 Sep;66(9):5453–5463. doi: 10.1128/jvi.66.9.5453-5463.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Imbalzano A. N., Shepard A. A., DeLuca N. A. Functional relevance of specific interactions between herpes simplex virus type 1 ICP4 and sequences from the promoter-regulatory domain of the viral thymidine kinase gene. J Virol. 1990 Jun;64(6):2620–2631. doi: 10.1128/jvi.64.6.2620-2631.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Jamieson D. R., Robinson L. H., Daksis J. I., Nicholl M. J., Preston C. M. Quiescent viral genomes in human fibroblasts after infection with herpes simplex virus type 1 Vmw65 mutants. J Gen Virol. 1995 Jun;76(Pt 6):1417–1431. doi: 10.1099/0022-1317-76-6-1417. [DOI] [PubMed] [Google Scholar]
  51. Johnson P. A., Everett R. D. The control of herpes simplex virus type-1 late gene transcription: a 'TATA-box'/cap site region is sufficient for fully efficient regulated activity. Nucleic Acids Res. 1986 Nov 11;14(21):8247–8264. doi: 10.1093/nar/14.21.8247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Kattar-Cooley P., Wilcox K. W. Characterization of the DNA-binding properties of herpes simplex virus regulatory protein ICP4. J Virol. 1989 Feb;63(2):696–704. doi: 10.1128/jvi.63.2.696-704.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Kibler P. K., Duncan J., Keith B. D., Hupel T., Smiley J. R. Regulation of herpes simplex virus true late gene expression: sequences downstream from the US11 TATA box inhibit expression from an unreplicated template. J Virol. 1991 Dec;65(12):6749–6760. doi: 10.1128/jvi.65.12.6749-6760.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Koop K. E., Duncan J., Smiley J. R. Binding sites for the herpes simplex virus immediate-early protein ICP4 impose an increased dependence on viral DNA replication on simple model promoters located in the viral genome. J Virol. 1993 Dec;67(12):7254–7263. doi: 10.1128/jvi.67.12.7254-7263.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Kristie T. M., Roizman B. DNA-binding site of major regulatory protein alpha 4 specifically associated with promoter-regulatory domains of alpha genes of herpes simplex virus type 1. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4700–4704. doi: 10.1073/pnas.83.13.4700. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Leib D. A., Coen D. M., Bogard C. L., Hicks K. A., Yager D. R., Knipe D. M., Tyler K. L., Schaffer P. A. Immediate-early regulatory gene mutants define different stages in the establishment and reactivation of herpes simplex virus latency. J Virol. 1989 Feb;63(2):759–768. doi: 10.1128/jvi.63.2.759-768.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Leopardi R., Michael N., Roizman B. Repression of the herpes simplex virus 1 alpha 4 gene by its gene product (ICP4) within the context of the viral genome is conditioned by the distance and stereoaxial alignment of the ICP4 DNA binding site relative to the TATA box. J Virol. 1995 May;69(5):3042–3048. doi: 10.1128/jvi.69.5.3042-3048.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Mackem S., Roizman B. Differentiation between alpha promoter and regulator regions of herpes simplex virus 1: the functional domains and sequence of a movable alpha regulator. Proc Natl Acad Sci U S A. 1982 Aug;79(16):4917–4921. doi: 10.1073/pnas.79.16.4917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Mackem S., Roizman B. Regulation of alpha genes of herpes simplex virus: the alpha 27 gene promoter-thymidine kinase chimera is positively regulated in converted L cells. J Virol. 1982 Sep;43(3):1015–1023. doi: 10.1128/jvi.43.3.1015-1023.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. 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]
  61. Macleod D., Charlton J., Mullins J., Bird A. P. Sp1 sites in the mouse aprt gene promoter are required to prevent methylation of the CpG island. Genes Dev. 1994 Oct 1;8(19):2282–2292. doi: 10.1101/gad.8.19.2282. [DOI] [PubMed] [Google Scholar]
  62. McCarthy A. M., McMahan L., Schaffer P. A. Herpes simplex virus type 1 ICP27 deletion mutants exhibit altered patterns of transcription and are DNA deficient. J Virol. 1989 Jan;63(1):18–27. doi: 10.1128/jvi.63.1.18-27.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. McKnight S., Tjian R. Transcriptional selectivity of viral genes in mammalian cells. Cell. 1986 Sep 12;46(6):795–805. doi: 10.1016/0092-8674(86)90061-9. [DOI] [PubMed] [Google Scholar]
  64. Mellon P., Parker V., Gluzman Y., Maniatis T. Identification of DNA sequences required for transcription of the human alpha 1-globin gene in a new SV40 host-vector system. Cell. 1981 Dec;27(2 Pt 1):279–288. doi: 10.1016/0092-8674(81)90411-6. [DOI] [PubMed] [Google Scholar]
  65. Muller M. T. Binding of the herpes simplex virus immediate-early gene product ICP4 to its own transcription start site. J Virol. 1987 Mar;61(3):858–865. doi: 10.1128/jvi.61.3.858-865.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. O'Hare P., Goding C. R., Haigh A. Direct combinatorial interaction between a herpes simplex virus regulatory protein and a cellular octamer-binding factor mediates specific induction of virus immediate-early gene expression. EMBO J. 1988 Dec 20;7(13):4231–4238. doi: 10.1002/j.1460-2075.1988.tb03320.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. 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]
  68. Panning B., Smiley J. R. Regulation of cellular genes transduced by herpes simplex virus. J Virol. 1989 May;63(5):1929–1937. doi: 10.1128/jvi.63.5.1929-1937.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Paterson T., Everett R. D. Mutational dissection of the HSV-1 immediate-early protein Vmw175 involved in transcriptional transactivation and repression. Virology. 1988 Sep;166(1):186–196. doi: 10.1016/0042-6822(88)90160-2. [DOI] [PubMed] [Google Scholar]
  70. Paterson T., Everett R. D. The regions of the herpes simplex virus type 1 immediate early protein Vmw175 required for site specific DNA binding closely correspond to those involved in transcriptional regulation. Nucleic Acids Res. 1988 Dec 9;16(23):11005–11025. doi: 10.1093/nar/16.23.11005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Poffenberger K. L., Raichlen P. E., Herman R. C. In vitro characterization of a herpes simplex virus type 1 ICP22 deletion mutant. Virus Genes. 1993 Jun;7(2):171–186. doi: 10.1007/BF01702397. [DOI] [PubMed] [Google Scholar]
  72. Post L. E., Roizman B. A generalized technique for deletion of specific genes in large genomes: alpha gene 22 of herpes simplex virus 1 is not essential for growth. Cell. 1981 Jul;25(1):227–232. doi: 10.1016/0092-8674(81)90247-6. [DOI] [PubMed] [Google Scholar]
  73. Preston C. M., Frame M. C., Campbell M. E. A complex formed between cell components and an HSV structural polypeptide binds to a viral immediate early gene regulatory DNA sequence. Cell. 1988 Feb 12;52(3):425–434. doi: 10.1016/s0092-8674(88)80035-7. [DOI] [PubMed] [Google Scholar]
  74. Purves F. C., Ogle W. O., Roizman B. Processing of the herpes simplex virus regulatory protein alpha 22 mediated by the UL13 protein kinase determines the accumulation of a subset of alpha and gamma mRNAs and proteins in infected cells. Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6701–6705. doi: 10.1073/pnas.90.14.6701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  75. Purves F. C., Roizman B. The UL13 gene of herpes simplex virus 1 encodes the functions for posttranslational processing associated with phosphorylation of the regulatory protein alpha 22. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7310–7314. doi: 10.1073/pnas.89.16.7310. [DOI] [PMC free article] [PubMed] [Google Scholar]
  76. Rice S. A., Long M. C., Lam V., Schaffer P. A., Spencer C. A. Herpes simplex virus immediate-early protein ICP22 is required for viral modification of host RNA polymerase II and establishment of the normal viral transcription program. J Virol. 1995 Sep;69(9):5550–5559. doi: 10.1128/jvi.69.9.5550-5559.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. Rivera-Gonzalez R., Imbalzano A. N., Gu B., Deluca N. A. The role of ICP4 repressor activity in temporal expression of the IE-3 and latency-associated transcript promoters during HSV-1 infection. Virology. 1994 Aug 1;202(2):550–564. doi: 10.1006/viro.1994.1377. [DOI] [PubMed] [Google Scholar]
  78. Roberts M. S., Boundy A., O'Hare P., Pizzorno M. C., Ciufo D. M., Hayward G. S. Direct correlation between a negative autoregulatory response element at the cap site of the herpes simplex virus type 1 IE175 (alpha 4) promoter and a specific binding site for the IE175 (ICP4) protein. J Virol. 1988 Nov;62(11):4307–4320. doi: 10.1128/jvi.62.11.4307-4320.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  79. Russell J., Stow N. D., Stow E. C., Preston C. M. Herpes simplex virus genes involved in latency in vitro. J Gen Virol. 1987 Dec;68(Pt 12):3009–3018. doi: 10.1099/0022-1317-68-12-3009. [DOI] [PubMed] [Google Scholar]
  80. Sacks W. R., Schaffer P. A. Deletion mutants in the gene encoding the herpes simplex virus type 1 immediate-early protein ICP0 exhibit impaired growth in cell culture. J Virol. 1987 Mar;61(3):829–839. doi: 10.1128/jvi.61.3.829-839.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  81. Sears A. E., Halliburton I. W., Meignier B., Silver S., Roizman B. Herpes simplex virus 1 mutant deleted in the alpha 22 gene: growth and gene expression in permissive and restrictive cells and establishment of latency in mice. J Virol. 1985 Aug;55(2):338–346. doi: 10.1128/jvi.55.2.338-346.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  82. Shepard A. A., Imbalzano A. N., DeLuca N. A. Separation of primary structural components conferring autoregulation, transactivation, and DNA-binding properties to the herpes simplex virus transcriptional regulatory protein ICP4. J Virol. 1989 Sep;63(9):3714–3728. doi: 10.1128/jvi.63.9.3714-3728.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  83. Smiley J. R., Duncan J. The herpes simplex virus type 1 immediate-early polypeptide ICP4 is required for expression of globin genes located in the viral genome. Virology. 1992 Sep;190(1):538–541. doi: 10.1016/0042-6822(92)91249-t. [DOI] [PubMed] [Google Scholar]
  84. Smiley J. R., Johnson D. C., Pizer L. I., Everett R. D. The ICP4 binding sites in the herpes simplex virus type 1 glycoprotein D (gD) promoter are not essential for efficient gD transcription during virus infection. J Virol. 1992 Feb;66(2):623–631. doi: 10.1128/jvi.66.2.623-631.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  85. Smiley J. R., Smibert C., Everett R. D. Expression of a cellular gene cloned in herpes simplex virus: rabbit beta-globin is regulated as an early viral gene in infected fibroblasts. J Virol. 1987 Aug;61(8):2368–2377. doi: 10.1128/jvi.61.8.2368-2377.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  86. Smith C. A., Bates P., Rivera-Gonzalez R., Gu B., DeLuca N. A. ICP4, the major transcriptional regulatory protein of herpes simplex virus type 1, forms a tripartite complex with TATA-binding protein and TFIIB. J Virol. 1993 Aug;67(8):4676–4687. doi: 10.1128/jvi.67.8.4676-4687.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  87. Stamatoyannopoulos J. A., Goodwin A., Joyce T., Lowrey C. H. NF-E2 and GATA binding motifs are required for the formation of DNase I hypersensitive site 4 of the human beta-globin locus control region. EMBO J. 1995 Jan 3;14(1):106–116. doi: 10.1002/j.1460-2075.1995.tb06980.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  88. Stow N. D., Stow E. C. Isolation and characterization of a herpes simplex virus type 1 mutant containing a deletion within the gene encoding the immediate early polypeptide Vmw110. J Gen Virol. 1986 Dec;67(Pt 12):2571–2585. doi: 10.1099/0022-1317-67-12-2571. [DOI] [PubMed] [Google Scholar]
  89. Tazi J., Bird A. Alternative chromatin structure at CpG islands. Cell. 1990 Mar 23;60(6):909–920. doi: 10.1016/0092-8674(90)90339-g. [DOI] [PubMed] [Google Scholar]
  90. Treisman R., Green M. R., Maniatis T. cis and trans activation of globin gene transcription in transient assays. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7428–7432. doi: 10.1073/pnas.80.24.7428. [DOI] [PMC free article] [PubMed] [Google Scholar]
  91. Triezenberg S. J., LaMarco K. L., McKnight S. L. Evidence of DNA: protein interactions that mediate HSV-1 immediate early gene activation by VP16. Genes Dev. 1988 Jun;2(6):730–742. doi: 10.1101/gad.2.6.730. [DOI] [PubMed] [Google Scholar]
  92. Umene K. Conversion of a fraction of the unique sequence to part of the inverted repeats in the S component of the herpes simplex virus type 1 genome. J Gen Virol. 1986 Jun;67(Pt 6):1035–1048. doi: 10.1099/0022-1317-67-6-1035. [DOI] [PubMed] [Google Scholar]
  93. Vyas P., Vickers M. A., Simmons D. L., Ayyub H., Craddock C. F., Higgs D. R. Cis-acting sequences regulating expression of the human alpha-globin cluster lie within constitutively open chromatin. Cell. 1992 May 29;69(5):781–793. doi: 10.1016/0092-8674(92)90290-s. [DOI] [PubMed] [Google Scholar]
  94. Ward P. L., Roizman B. Herpes simplex genes: the blueprint of a successful human pathogen. Trends Genet. 1994 Aug;10(8):267–274. doi: 10.1016/0168-9525(90)90009-u. [DOI] [PubMed] [Google Scholar]
  95. 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]
  96. Wu C. L., Wilcox K. W. Codons 262 to 490 from the herpes simplex virus ICP4 gene are sufficient to encode a sequence-specific DNA binding protein. Nucleic Acids Res. 1990 Feb 11;18(3):531–538. doi: 10.1093/nar/18.3.531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  97. Yao F., Schaffer P. A. An activity specified by the osteosarcoma line U2OS can substitute functionally for ICP0, a major regulatory protein of herpes simplex virus type 1. J Virol. 1995 Oct;69(10):6249–6258. doi: 10.1128/jvi.69.10.6249-6258.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES