Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1996 Dec;70(12):8590–8605. doi: 10.1128/jvi.70.12.8590-8605.1996

Synergistic interactions between overlapping binding sites for the serum response factor and ELK-1 proteins mediate both basal enhancement and phorbol ester responsiveness of primate cytomegalovirus major immediate-early promoters in monocyte and T-lymphocyte cell types.

Y J Chan 1, C J Chiou 1, Q Huang 1, G S Hayward 1
PMCID: PMC190952  PMID: 8970984

Abstract

Cytomegalovirus (CMV) infection is nonpermissive or persistent in many lymphoid and myeloid cell types but can be activated in differentiated macrophages. We have shown elsewhere that both the major immediate-early gene (MIE) and lytic cycle infectious progeny virus expression can be induced in otherwise nonpermissive monocyte-like U-937 cell cultures infected with either human CMV (HCMV) or simian CMV (SCMV) by treatment with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). Two multicopy basal enhancer motifs within the SCMV MIE enhancer, namely, 11 copies of the 16-bp cyclic AMP response element (CRE) and 3 copies of novel 17-bp serum response factor (SRF) binding sites referred to as the SNE (SRF/NFkappaB-like element), as well as four classical NFkappaB sites within the HCMV version, contribute to TPA responsiveness in transient assays in monocyte and T-cell types. The SCMV SNE sites contain potential overlapping core recognition binding motifs for SRF, Rel/NFkappaB, ETS, and YY1 class transcription factors but fail to respond to either serum or tumor necrosis factor alpha. Therefore, to evaluate the mechanism of TPA responsiveness of the SNE motifs and of a related 16-bp SEE (SRF/ETS element) motif found in the HCMV and chimpanzee CMV MIE enhancers, we have examined the functional responses and protein binding properties of multimerized wild-type and mutant elements added upstream to the SCMV MIE or simian virus 40 minimal promoter regions in the U-937, K-562, HL-60, THP-1, and Jurkat cell lines. Unlike classical NFkappaB sites, neither the SNE nor the SEE motif responded to phosphatase inhibition by okadaic acid. However, the TPA responsiveness of both CMV elements proved to involve synergistic interactions between the core SRF binding site (CCATATATGG) and the adjacent inverted ETS binding motifs (TTCC), which correlated directly with formation of a bound tripartite complex containing both the cellular SRF and ELK-1 proteins. This protein complex was more abundant in U-937, K-562, and HeLa cell extracts than in Raji, HF, BALB/c 3T3, or HL-60 cells, but the binding activity was altered only twofold after TPA treatment. A 40-fold stimulation of chloramphenicol acetyltransferase activity mediated by four tandem repeats of the SNE could be induced within 2 h (and up to 250-fold within 6 h) after addition of TPA in DNA-transfected U-937 cells, indicating that the stimulation appeared likely to be a true protein kinase C-mediated signal transduction event rather than a differentiation response. Slight differences in the sequence of the core SRF binding site compared with that of the classical c-Fos promoter serum response element, together with differences in the spacing between the SRF and ETS motifs, appear to account for the inability of the SCMV SNEs to respond to serum induction.

Full Text

The Full Text of this article is available as a PDF (604.1 KB).

Selected References

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

  1. Alcendor D. J., Barry P. A., Pratt-Lowe E., Luciw P. A. Analysis of the rhesus cytomegalovirus immediate-early gene promoter. Virology. 1993 Jun;194(2):815–821. doi: 10.1006/viro.1993.1323. [DOI] [PubMed] [Google Scholar]
  2. Bellas R. E., Hopkins N., Li Y. The NF-kappa B binding site is necessary for efficient replication of simian immunodeficiency virus of macaques in primary macrophages but not in T cells in vitro. J Virol. 1993 May;67(5):2908–2913. doi: 10.1128/jvi.67.5.2908-2913.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bhat N. K., Thompson C. B., Lindsten T., June C. H., Fujiwara S., Koizumi S., Fisher R. J., Papas T. S. Reciprocal expression of human ETS1 and ETS2 genes during T-cell activation: regulatory role for the protooncogene ETS1. Proc Natl Acad Sci U S A. 1990 May;87(10):3723–3727. doi: 10.1073/pnas.87.10.3723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Blank V., Kourilsky P., Israël A. NF-kappa B and related proteins: Rel/dorsal homologies meet ankyrin-like repeats. Trends Biochem Sci. 1992 Apr;17(4):135–140. doi: 10.1016/0968-0004(92)90321-y. [DOI] [PubMed] [Google Scholar]
  5. Boshart M., Weber F., Jahn G., Dorsch-Häsler K., Fleckenstein B., Schaffner W. A very strong enhancer is located upstream of an immediate early gene of human cytomegalovirus. Cell. 1985 Jun;41(2):521–530. doi: 10.1016/s0092-8674(85)80025-8. [DOI] [PubMed] [Google Scholar]
  6. Büscher D., Hipskind R. A., Krautwald S., Reimann T., Baccarini M. Ras-dependent and -independent pathways target the mitogen-activated protein kinase network in macrophages. Mol Cell Biol. 1995 Jan;15(1):466–475. doi: 10.1128/mcb.15.1.466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chan Y. J., Tseng W. P., Hayward G. S. Two distinct upstream regulatory domains containing multicopy cellular transcription factor binding sites provide basal repression and inducible enhancer characteristics to the immediate-early IES (US3) promoter from human cytomegalovirus. J Virol. 1996 Aug;70(8):5312–5328. doi: 10.1128/jvi.70.8.5312-5328.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chang Y. N., Crawford S., Stall J., Rawlins D. R., Jeang K. T., Hayward G. S. The palindromic series I repeats in the simian cytomegalovirus major immediate-early promoter behave as both strong basal enhancers and cyclic AMP response elements. J Virol. 1990 Jan;64(1):264–277. doi: 10.1128/jvi.64.1.264-277.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chang Y. N., Jeang K. T., Chiou C. J., Chan Y. J., Pizzorno M., Hayward G. S. Identification of a large bent DNA domain and binding sites for serum response factor adjacent to the NFI repeat cluster and enhancer region in the major IE94 promoter from simian cytomegalovirus. J Virol. 1993 Jan;67(1):516–529. doi: 10.1128/jvi.67.1.516-529.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Chiou C. J., Zong J., Waheed I., Hayward G. S. Identification and mapping of dimerization and DNA-binding domains in the C terminus of the IE2 regulatory protein of human cytomegalovirus. J Virol. 1993 Oct;67(10):6201–6214. doi: 10.1128/jvi.67.10.6201-6214.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Christy B. A., Lau L. F., Nathans D. A gene activated in mouse 3T3 cells by serum growth factors encodes a protein with "zinc finger" sequences. Proc Natl Acad Sci U S A. 1988 Nov;85(21):7857–7861. doi: 10.1073/pnas.85.21.7857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Cohen P., Klumpp S., Schelling D. L. An improved procedure for identifying and quantitating protein phosphatases in mammalian tissues. FEBS Lett. 1989 Jul 3;250(2):596–600. doi: 10.1016/0014-5793(89)80803-8. [DOI] [PubMed] [Google Scholar]
  13. Dalton S., Treisman R. Characterization of SAP-1, a protein recruited by serum response factor to the c-fos serum response element. Cell. 1992 Feb 7;68(3):597–612. doi: 10.1016/0092-8674(92)90194-h. [DOI] [PubMed] [Google Scholar]
  14. Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Dutko F. J., Oldstone M. B. Cytomegalovirus causes a latent infection in undifferentiated cells and is activated by induction of cell differentiation. J Exp Med. 1981 Nov 1;154(5):1636–1651. doi: 10.1084/jem.154.5.1636. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Fietze E., Prösch S., Reinke P., Stein J., Döcke W. D., Staffa G., Löning S., Devaux S., Emmrich F., von Baehr R. Cytomegalovirus infection in transplant recipients. The role of tumor necrosis factor. Transplantation. 1994 Sep 27;58(6):675–680. [PubMed] [Google Scholar]
  17. Fish K. N., Depto A. S., Moses A. V., Britt W., Nelson J. A. Growth kinetics of human cytomegalovirus are altered in monocyte-derived macrophages. J Virol. 1995 Jun;69(6):3737–3743. doi: 10.1128/jvi.69.6.3737-3743.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Forbes B. A., Bonville C. A., Dock N. L. The effects of a promoter of cell differentiation and selected hormones on human cytomegalovirus infection using an in vitro cell system. J Infect Dis. 1990 Jul;162(1):39–45. doi: 10.1093/infdis/162.1.39. [DOI] [PubMed] [Google Scholar]
  19. Ghazal P., DeMattei C., Giulietti E., Kliewer S. A., Umesono K., Evans R. M. Retinoic acid receptors initiate induction of the cytomegalovirus enhancer in embryonal cells. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7630–7634. doi: 10.1073/pnas.89.16.7630. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ghazal P., Lubon H., Fleckenstein B., Hennighausen L. Binding of transcription factors and creation of a large nucleoprotein complex on the human cytomegalovirus enhancer. Proc Natl Acad Sci U S A. 1987 Jun;84(11):3658–3662. doi: 10.1073/pnas.84.11.3658. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Graham R., Gilman M. Distinct protein targets for signals acting at the c-fos serum response element. Science. 1991 Jan 11;251(4990):189–192. doi: 10.1126/science.1898992. [DOI] [PubMed] [Google Scholar]
  22. Gönczöl E., Andrews P. W., Plotkin S. A. Cytomegalovirus replicates in differentiated but not in undifferentiated human embryonal carcinoma cells. Science. 1984 Apr 13;224(4645):159–161. doi: 10.1126/science.6322309. [DOI] [PubMed] [Google Scholar]
  23. Hermiston T. W., Malone C. L., Witte P. R., Stinski M. F. Identification and characterization of the human cytomegalovirus immediate-early region 2 gene that stimulates gene expression from an inducible promoter. J Virol. 1987 Oct;61(10):3214–3221. doi: 10.1128/jvi.61.10.3214-3221.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Herrera R. E., Shaw P. E., Nordheim A. Occupation of the c-fos serum response element in vivo by a multi-protein complex is unaltered by growth factor induction. Nature. 1989 Jul 6;340(6228):68–70. doi: 10.1038/340068a0. [DOI] [PubMed] [Google Scholar]
  25. Hilfinger J. M., Clark N., Smith M., Robinson K., Markovitz D. M. Differential regulation of the human immunodeficiency virus type 2 enhancer in monocytes at various stages of differentiation. J Virol. 1993 Jul;67(7):4448–4453. doi: 10.1128/jvi.67.7.4448-4453.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Hill C. S., Wynne J., Treisman R. Serum-regulated transcription by serum response factor (SRF): a novel role for the DNA binding domain. EMBO J. 1994 Nov 15;13(22):5421–5432. doi: 10.1002/j.1460-2075.1994.tb06877.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Hipskind R. A., Büscher D., Nordheim A., Baccarini M. Ras/MAP kinase-dependent and -independent signaling pathways target distinct ternary complex factors. Genes Dev. 1994 Aug 1;8(15):1803–1816. doi: 10.1101/gad.8.15.1803. [DOI] [PubMed] [Google Scholar]
  28. Hipskind R. A., Rao V. N., Mueller C. G., Reddy E. S., Nordheim A. Ets-related protein Elk-1 is homologous to the c-fos regulatory factor p62TCF. Nature. 1991 Dec 19;354(6354):531–534. doi: 10.1038/354531a0. [DOI] [PubMed] [Google Scholar]
  29. Hunninghake G. W., Monick M. M., Liu B., Stinski M. F. The promoter-regulatory region of the major immediate-early gene of human cytomegalovirus responds to T-lymphocyte stimulation and contains functional cyclic AMP-response elements. J Virol. 1989 Jul;63(7):3026–3033. doi: 10.1128/jvi.63.7.3026-3033.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Ibanez C. E., Schrier R., Ghazal P., Wiley C., Nelson J. A. Human cytomegalovirus productively infects primary differentiated macrophages. J Virol. 1991 Dec;65(12):6581–6588. doi: 10.1128/jvi.65.12.6581-6588.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Janknecht R., Zinck R., Ernst W. H., Nordheim A. Functional dissection of the transcription factor Elk-1. Oncogene. 1994 Apr;9(4):1273–1278. [PubMed] [Google Scholar]
  32. Jeang K. T., Cho M. S., Hayward G. S. Abundant constitutive expression of the immediate-early 94K protein from cytomegalovirus (Colburn) in a DNA-transfected mouse cell line. Mol Cell Biol. 1984 Oct;4(10):2214–2223. doi: 10.1128/mcb.4.10.2214. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Jeang K. T., Gibson W. A cycloheximide-enhanced protein in cytomegalovirus-infected cells. Virology. 1980 Dec;107(2):362–374. doi: 10.1016/0042-6822(80)90304-9. [DOI] [PubMed] [Google Scholar]
  34. Jeang K. T., Rawlins D. R., Rosenfeld P. J., Shero J. H., Kelly T. J., Hayward G. S. Multiple tandemly repeated binding sites for cellular nuclear factor 1 that surround the major immediate-early promoters of simian and human cytomegalovirus. J Virol. 1987 May;61(5):1559–1570. doi: 10.1128/jvi.61.5.1559-1570.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Johansen F. E., Prywes R. Two pathways for serum regulation of the c-fos serum response element require specific sequence elements and a minimal domain of serum response factor. Mol Cell Biol. 1994 Sep;14(9):5920–5928. doi: 10.1128/mcb.14.9.5920. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Karim F. D., Urness L. D., Thummel C. S., Klemsz M. J., McKercher S. R., Celada A., Van Beveren C., Maki R. A., Gunther C. V., Nye J. A. The ETS-domain: a new DNA-binding motif that recognizes a purine-rich core DNA sequence. Genes Dev. 1990 Sep;4(9):1451–1453. doi: 10.1101/gad.4.9.1451. [DOI] [PubMed] [Google Scholar]
  37. Kondo K., Kaneshima H., Mocarski E. S. Human cytomegalovirus latent infection of granulocyte-macrophage progenitors. Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):11879–11883. doi: 10.1073/pnas.91.25.11879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. LaFemina R., Hayward G. S. Constitutive and retinoic acid-inducible expression of cytomegalovirus immediate-early genes in human teratocarcinoma cells. J Virol. 1986 May;58(2):434–440. doi: 10.1128/jvi.58.2.434-440.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. LaMarco K. L., McKnight S. L. Purification of a set of cellular polypeptides that bind to the purine-rich cis-regulatory element of herpes simplex virus immediate early genes. Genes Dev. 1989 Sep;3(9):1372–1383. doi: 10.1101/gad.3.9.1372. [DOI] [PubMed] [Google Scholar]
  40. LaMarco K., Thompson C. C., Byers B. P., Walton E. M., McKnight S. L. Identification of Ets- and notch-related subunits in GA binding protein. Science. 1991 Aug 16;253(5021):789–792. doi: 10.1126/science.1876836. [DOI] [PubMed] [Google Scholar]
  41. Lafemina R. L., Hayward G. S. Differences in cell-type-specific blocks to immediate early gene expression and DNA replication of human, simian and murine cytomegalovirus. J Gen Virol. 1988 Feb;69(Pt 2):355–374. doi: 10.1099/0022-1317-69-2-355. [DOI] [PubMed] [Google Scholar]
  42. Lafemina R. L., Pizzorno M. C., Mosca J. D., Hayward G. S. Expression of the acidic nuclear immediate-early protein (IE1) of human cytomegalovirus in stable cell lines and its preferential association with metaphase chromosomes. Virology. 1989 Oct;172(2):584–600. doi: 10.1016/0042-6822(89)90201-8. [DOI] [PubMed] [Google Scholar]
  43. Lang D., Stamminger T. The 86-kilodalton IE-2 protein of human cytomegalovirus is a sequence-specific DNA-binding protein that interacts directly with the negative autoregulatory response element located near the cap site of the IE-1/2 enhancer-promoter. J Virol. 1993 Jan;67(1):323–331. doi: 10.1128/jvi.67.1.323-331.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Lathey J. L., Spector S. A. Unrestricted replication of human cytomegalovirus in hydrocortisone-treated macrophages. J Virol. 1991 Nov;65(11):6371–6375. doi: 10.1128/jvi.65.11.6371-6375.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Lieberman P. M., Hardwick J. M., Hayward S. D. Responsiveness of the Epstein-Barr virus NotI repeat promoter to the Z transactivator is mediated in a cell-type-specific manner by two independent signal regions. J Virol. 1989 Jul;63(7):3040–3050. doi: 10.1128/jvi.63.7.3040-3050.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Lieberman P. M., Hardwick J. M., Sample J., Hayward G. S., Hayward S. D. The zta transactivator involved in induction of lytic cycle gene expression in Epstein-Barr virus-infected lymphocytes binds to both AP-1 and ZRE sites in target promoter and enhancer regions. J Virol. 1990 Mar;64(3):1143–1155. doi: 10.1128/jvi.64.3.1143-1155.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Liu B., Stinski M. F. Human cytomegalovirus contains a tegument protein that enhances transcription from promoters with upstream ATF and AP-1 cis-acting elements. J Virol. 1992 Jul;66(7):4434–4444. doi: 10.1128/jvi.66.7.4434-4444.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Liu R., Baillie J., Sissons J. G., Sinclair J. H. The transcription factor YY1 binds to negative regulatory elements in the human cytomegalovirus major immediate early enhancer/promoter and mediates repression in non-permissive cells. Nucleic Acids Res. 1994 Jul 11;22(13):2453–2459. doi: 10.1093/nar/22.13.2453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Macleod K., Leprince D., Stehelin D. The ets gene family. Trends Biochem Sci. 1992 Jul;17(7):251–256. doi: 10.1016/0968-0004(92)90404-w. [DOI] [PubMed] [Google Scholar]
  50. Marais R., Wynne J., Treisman R. The SRF accessory protein Elk-1 contains a growth factor-regulated transcriptional activation domain. Cell. 1993 Apr 23;73(2):381–393. doi: 10.1016/0092-8674(93)90237-k. [DOI] [PubMed] [Google Scholar]
  51. Nabel G., Baltimore D. An inducible transcription factor activates expression of human immunodeficiency virus in T cells. Nature. 1987 Apr 16;326(6114):711–713. doi: 10.1038/326711a0. [DOI] [PubMed] [Google Scholar]
  52. Nelson J. A., Reynolds-Kohler C., Smith B. A. Negative and positive regulation by a short segment in the 5'-flanking region of the human cytomegalovirus major immediate-early gene. Mol Cell Biol. 1987 Nov;7(11):4125–4129. doi: 10.1128/mcb.7.11.4125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Niller H. H., Hennighausen L. Phytohemagglutinin-induced activity of cyclic AMP (cAMP) response elements from cytomegalovirus is reduced by cyclosporine and synergistically enhanced by cAMP. J Virol. 1990 May;64(5):2388–2391. doi: 10.1128/jvi.64.5.2388-2391.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Norman C., Runswick M., Pollock R., Treisman R. Isolation and properties of cDNA clones encoding SRF, a transcription factor that binds to the c-fos serum response element. Cell. 1988 Dec 23;55(6):989–1003. doi: 10.1016/0092-8674(88)90244-9. [DOI] [PubMed] [Google Scholar]
  55. Pizzorno M. C., Hayward G. S. The IE2 gene products of human cytomegalovirus specifically down-regulate expression from the major immediate-early promoter through a target sequence located near the cap site. J Virol. 1990 Dec;64(12):6154–6165. doi: 10.1128/jvi.64.12.6154-6165.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. 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]
  57. Pizzorno M. C., O'Hare P., Sha L., LaFemina R. L., Hayward G. S. trans-activation and autoregulation of gene expression by the immediate-early region 2 gene products of human cytomegalovirus. J Virol. 1988 Apr;62(4):1167–1179. doi: 10.1128/jvi.62.4.1167-1179.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Price M. A., Rogers A. E., Treisman R. Comparative analysis of the ternary complex factors Elk-1, SAP-1a and SAP-2 (ERP/NET). EMBO J. 1995 Jun 1;14(11):2589–2601. doi: 10.1002/j.1460-2075.1995.tb07257.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Rice G. P., Schrier R. D., Oldstone M. B. Cytomegalovirus infects human lymphocytes and monocytes: virus expression is restricted to immediate-early gene products. Proc Natl Acad Sci U S A. 1984 Oct;81(19):6134–6138. doi: 10.1073/pnas.81.19.6134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. 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]
  61. Ryan W. A., Jr, Franza B. R., Jr, Gilman M. Z. Two distinct cellular phosphoproteins bind to the c-fos serum response element. EMBO J. 1989 Jun;8(6):1785–1792. doi: 10.1002/j.1460-2075.1989.tb03572.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Sambucetti L. C., Cherrington J. M., Wilkinson G. W., Mocarski E. S. NF-kappa B activation of the cytomegalovirus enhancer is mediated by a viral transactivator and by T cell stimulation. EMBO J. 1989 Dec 20;8(13):4251–4258. doi: 10.1002/j.1460-2075.1989.tb08610.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Schrier R. D., Nelson J. A., Oldstone M. B. Detection of human cytomegalovirus in peripheral blood lymphocytes in a natural infection. Science. 1985 Nov 29;230(4729):1048–1051. doi: 10.1126/science.2997930. [DOI] [PubMed] [Google Scholar]
  64. Schröter H., Mueller C. G., Meese K., Nordheim A. Synergism in ternary complex formation between the dimeric glycoprotein p67SRF, polypeptide p62TCF and the c-fos serum response element. EMBO J. 1990 Apr;9(4):1123–1130. doi: 10.1002/j.1460-2075.1990.tb08218.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Seth A., Ascione R., Fisher R. J., Mavrothalassitis G. J., Bhat N. K., Papas T. S. The ets gene family. Cell Growth Differ. 1992 May;3(5):327–334. [PubMed] [Google Scholar]
  66. Sharrocks A. D., von Hesler F., Shaw P. E. The identification of elements determining the different DNA binding specificities of the MADS box proteins p67SRF and RSRFC4. Nucleic Acids Res. 1993 Jan 25;21(2):215–221. doi: 10.1093/nar/21.2.215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Shaw P. E., Schröter H., Nordheim A. The ability of a ternary complex to form over the serum response element correlates with serum inducibility of the human c-fos promoter. Cell. 1989 Feb 24;56(4):563–572. doi: 10.1016/0092-8674(89)90579-5. [DOI] [PubMed] [Google Scholar]
  68. Shore P., Sharrocks A. D. The transcription factors Elk-1 and serum response factor interact by direct protein-protein contacts mediated by a short region of Elk-1. Mol Cell Biol. 1994 May;14(5):3283–3291. doi: 10.1128/mcb.14.5.3283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Sinclair J. H., Baillie J., Bryant L. A., Taylor-Wiedeman J. A., Sissons J. G. Repression of human cytomegalovirus major immediate early gene expression in a monocytic cell line. J Gen Virol. 1992 Feb;73(Pt 2):433–435. doi: 10.1099/0022-1317-73-2-433. [DOI] [PubMed] [Google Scholar]
  70. Stamminger T., Fickenscher H., Fleckenstein B. Cell type-specific induction of the major immediate early enhancer of human cytomegalovirus by cyclic AMP. J Gen Virol. 1990 Jan;71(Pt 1):105–113. doi: 10.1099/0022-1317-71-1-105. [DOI] [PubMed] [Google Scholar]
  71. Stein J., Volk H. D., Liebenthal C., Krüger D. H., Prösch S. Tumour necrosis factor alpha stimulates the activity of the human cytomegalovirus major immediate early enhancer/promoter in immature monocytic cells. J Gen Virol. 1993 Nov;74(Pt 11):2333–2338. doi: 10.1099/0022-1317-74-11-2333. [DOI] [PubMed] [Google Scholar]
  72. Stenberg R. M., Fortney J., Barlow S. W., Magrane B. P., Nelson J. A., Ghazal P. Promoter-specific trans activation and repression by human cytomegalovirus immediate-early proteins involves common and unique protein domains. J Virol. 1990 Apr;64(4):1556–1565. doi: 10.1128/jvi.64.4.1556-1565.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Stenberg R. M., Thomsen D. R., Stinski M. F. Structural analysis of the major immediate early gene of human cytomegalovirus. J Virol. 1984 Jan;49(1):190–199. doi: 10.1128/jvi.49.1.190-199.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. Sun S. C., Maggirwar S. B., Harhaj E. Activation of NF-kappa B by phosphatase inhibitors involves the phosphorylation of I kappa B alpha at phosphatase 2A-sensitive sites. J Biol Chem. 1995 Aug 4;270(31):18347–18351. doi: 10.1074/jbc.270.31.18347. [DOI] [PubMed] [Google Scholar]
  75. Sundström C., Nilsson K. Establishment and characterization of a human histiocytic lymphoma cell line (U-937). Int J Cancer. 1976 May 15;17(5):565–577. doi: 10.1002/ijc.2910170504. [DOI] [PubMed] [Google Scholar]
  76. Taylor-Wiedeman J., Sissons J. G., Borysiewicz L. K., Sinclair J. H. Monocytes are a major site of persistence of human cytomegalovirus in peripheral blood mononuclear cells. J Gen Virol. 1991 Sep;72(Pt 9):2059–2064. doi: 10.1099/0022-1317-72-9-2059. [DOI] [PubMed] [Google Scholar]
  77. Taylor-Wiedeman J., Sissons P., Sinclair J. Induction of endogenous human cytomegalovirus gene expression after differentiation of monocytes from healthy carriers. J Virol. 1994 Mar;68(3):1597–1604. doi: 10.1128/jvi.68.3.1597-1604.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Thanos D., Maniatis T. NF-kappa B: a lesson in family values. Cell. 1995 Feb 24;80(4):529–532. doi: 10.1016/0092-8674(95)90506-5. [DOI] [PubMed] [Google Scholar]
  79. Thomsen D. R., Stenberg R. M., Goins W. F., Stinski M. F. Promoter-regulatory region of the major immediate early gene of human cytomegalovirus. Proc Natl Acad Sci U S A. 1984 Feb;81(3):659–663. doi: 10.1073/pnas.81.3.659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  80. Thévenin C., Kim S. J., Kehrl J. H. Inhibition of protein phosphatases by okadaic acid induces AP1 in human T cells. J Biol Chem. 1991 May 25;266(15):9363–9366. [PubMed] [Google Scholar]
  81. Treisman R. Identification of a protein-binding site that mediates transcriptional response of the c-fos gene to serum factors. Cell. 1986 Aug 15;46(4):567–574. doi: 10.1016/0092-8674(86)90882-2. [DOI] [PubMed] [Google Scholar]
  82. Treisman R. Ternary complex factors: growth factor regulated transcriptional activators. Curr Opin Genet Dev. 1994 Feb;4(1):96–101. doi: 10.1016/0959-437x(94)90097-3. [DOI] [PubMed] [Google Scholar]
  83. Wathen M. W., Stinski M. F. Temporal patterns of human cytomegalovirus transcription: mapping the viral RNAs synthesized at immediate early, early, and late times after infection. J Virol. 1982 Feb;41(2):462–477. doi: 10.1128/jvi.41.2.462-477.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  84. Weinshenker B. G., Wilton S., Rice G. P. Phorbol ester-induced differentiation permits productive human cytomegalovirus infection in a monocytic cell line. J Immunol. 1988 Mar 1;140(5):1625–1631. [PubMed] [Google Scholar]

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

RESOURCES