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. 1994 Jun;68(6):3943–3954. doi: 10.1128/jvi.68.6.3943-3954.1994

UL69 of human cytomegalovirus, an open reading frame with homology to ICP27 of herpes simplex virus, encodes a transactivator of gene expression.

M Winkler 1, S A Rice 1, T Stamminger 1
PMCID: PMC236900  PMID: 8189530

Abstract

The UL69 open reading frame of human cytomegalovirus (HCMV) is homologous to the immediate-early protein ICP27 of herpes simplex virus, an essential viral regulatory protein involved in the transition from early to late gene expression. Genes with homology to ICP27 have been detected in all subclasses of herpesviruses so far. While the respective proteins in alpha- and gammaherpesviruses have been defined as trans-regulatory molecules, nothing is known about these genes in betaherpesviruses. This study was therefore undertaken in order to investigate expression from the UL69 gene locus of HCMV. Northern (RNA) blot experiments revealed a complex pattern of transcripts that changed during the time course of the HCMV replicative cycle: two transcripts of 2.7 and 3.5 kb that were regulated differentially could be detected as early as 7 h after infection. However, these transcripts could not be detected in the presence of cycloheximide. Additional, larger transcripts were present exclusively at late times after infection. To analyze protein expression from the UL69 gene region, the UL69 open reading frame was expressed as a histidine-tagged protein in Escherichia coli. A specific antiserum was generated and used to detect the UL69 protein in HCMV-infected cells which revealed its localization within the intranuclear inclusions that are characteristic for HCMV infection. In cotransfection experiments, an HCMV true late promoter could not be activated by UL69, whereas an early promoter and several heterologous promoters were stimulated about 10-fold. Complementation studies showed that the UL69 protein cannot substitute for ICP27 in the context of the HSV infection, suggesting functional differences between these two proteins. In summary, these experiments define a novel regulatory protein encoded by HCMV that is expressed as an early-late gene and appears to exert a broad stimulatory effect on gene expression.

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Selected References

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

  1. Akrigg A., Wilkinson G. W., Oram J. D. The structure of the major immediate early gene of human cytomegalovirus strain AD169. Virus Res. 1985 Mar;2(2):107–121. doi: 10.1016/0168-1702(85)90242-4. [DOI] [PubMed] [Google Scholar]
  2. Albrecht J. C., Nicholas J., Biller D., Cameron K. R., Biesinger B., Newman C., Wittmann S., Craxton M. A., Coleman H., Fleckenstein B. Primary structure of the herpesvirus saimiri genome. J Virol. 1992 Aug;66(8):5047–5058. doi: 10.1128/jvi.66.8.5047-5058.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Anders D. G., Kidd J. R., Gibson W. Immunological characterization of an early cytomegalovirus single-strand DNA-binding protein with similarities to the HSV major DNA-binding protein. Virology. 1987 Dec;161(2):579–588. doi: 10.1016/0042-6822(87)90154-1. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Buisson M., Manet E., Trescol-Biemont M. C., Gruffat H., Durand B., Sergeant A. The Epstein-Barr virus (EBV) early protein EB2 is a posttranscriptional activator expressed under the control of EBV transcription factors EB1 and R. J Virol. 1989 Dec;63(12):5276–5284. doi: 10.1128/jvi.63.12.5276-5284.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. CRAIG J. M., MACAULEY J. C., WELLER T. H., WIRTH P. Isolation of intranuclear inclusion producing agents from infants with illnesses resembling cytomegalic inclusion disease. Proc Soc Exp Biol Med. 1957 Jan;94(1):4–12. doi: 10.3181/00379727-94-22841. [DOI] [PubMed] [Google Scholar]
  7. Cavallo T., Graves K., Cole N. L., Albrecht T. Cytomegalovirus: an ultrastructural study of the morphogenesis of nuclear inclusions in human cell culture. J Gen Virol. 1981 Sep;56(Pt 1):97–104. doi: 10.1099/0022-1317-56-1-97. [DOI] [PubMed] [Google Scholar]
  8. Chang C. P., Malone C. L., Stinski M. F. A human cytomegalovirus early gene has three inducible promoters that are regulated differentially at various times after infection. J Virol. 1989 Jan;63(1):281–290. doi: 10.1128/jvi.63.1.281-290.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chapman C. J., Harris J. D., Hardwicke M. A., Sandri-Goldin R. M., Collins M. K., Latchman D. S. Promoter-independent activation of heterologous virus gene expression by the herpes simplex virus immediate-early protein ICP27. Virology. 1992 Feb;186(2):573–578. doi: 10.1016/0042-6822(92)90023-i. [DOI] [PubMed] [Google Scholar]
  10. Chee M. S., Bankier A. T., Beck S., Bohni R., Brown C. M., Cerny R., Horsnell T., Hutchison C. A., 3rd, Kouzarides T., Martignetti J. A. Analysis of the protein-coding content of the sequence of human cytomegalovirus strain AD169. Curr Top Microbiol Immunol. 1990;154:125–169. doi: 10.1007/978-3-642-74980-3_6. [DOI] [PubMed] [Google Scholar]
  11. Chevallier-Greco A., Manet E., Chavrier P., Mosnier C., Daillie J., Sergeant A. Both Epstein-Barr virus (EBV)-encoded trans-acting factors, EB1 and EB2, are required to activate transcription from an EBV early promoter. EMBO J. 1986 Dec 1;5(12):3243–3249. doi: 10.1002/j.1460-2075.1986.tb04635.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Cho M. S., Milman G., Hayward S. D. A second Epstein-Barr virus early antigen gene in BamHI fragment M encodes a 48- to 50-kilodalton nuclear protein. J Virol. 1985 Dec;56(3):860–866. doi: 10.1128/jvi.56.3.860-866.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Colberg-Poley A. M., Santomenna L. D., Harlow P. P., Benfield P. A., Tenney D. J. Human cytomegalovirus US3 and UL36-38 immediate-early proteins regulate gene expression. J Virol. 1992 Jan;66(1):95–105. doi: 10.1128/jvi.66.1.95-105.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Defechereux P., Melen L., Baudoux L., Merville-Louis M. P., Rentier B., Piette J. Characterization of the regulatory functions of varicella-zoster virus open reading frame 4 gene product. J Virol. 1993 Jul;67(7):4379–4385. doi: 10.1128/jvi.67.7.4379-4385.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Demarchi J. M. Human cytomegalovirus DNA: restriction enzyme cleavage maps and map locations for immediate-early, early, and late RNAs. Virology. 1981 Oct 15;114(1):23–38. doi: 10.1016/0042-6822(81)90249-x. [DOI] [PubMed] [Google Scholar]
  16. Depto A. S., Stenberg R. M. Functional analysis of the true late human cytomegalovirus pp28 upstream promoter: cis-acting elements and viral trans-acting proteins necessary for promoter activation. J Virol. 1992 May;66(5):3241–3246. doi: 10.1128/jvi.66.5.3241-3246.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ellinger S., Mach M., Korn K., Jahn G. Cleavage and purification of prokaryotically expressed HIV gag and env fusion proteins for detection of HIV antibodies in the ELISA. Virology. 1991 Feb;180(2):811–813. doi: 10.1016/0042-6822(91)90097-u. [DOI] [PubMed] [Google Scholar]
  18. Everett R. D. The products of herpes simplex virus type 1 (HSV-1) immediate early genes 1, 2 and 3 can activate HSV-1 gene expression in trans. J Gen Virol. 1986 Nov;67(Pt 11):2507–2513. doi: 10.1099/0022-1317-67-11-2507. [DOI] [PubMed] [Google Scholar]
  19. Fickenscher H., Stamminger T., Rüger R., Fleckenstein B. The role of a repetitive palindromic sequence element in the human cytomegalovirus major immediate early enhancer. J Gen Virol. 1989 Jan;70(Pt 1):107–123. doi: 10.1099/0022-1317-70-1-107. [DOI] [PubMed] [Google Scholar]
  20. Fleckenstein B., Müller I., Collins J. Cloning of the complete human cytomegalovirus genome in cosmids. Gene. 1982 Apr;18(1):39–46. doi: 10.1016/0378-1119(82)90054-3. [DOI] [PubMed] [Google Scholar]
  21. Fong C. K. Ultrastructural localization of cytomegalovirus DNA synthesis in infected guinea-pig cells. J Gen Virol. 1982 Jun;60(Pt 2):235–245. doi: 10.1099/0022-1317-60-2-235. [DOI] [PubMed] [Google Scholar]
  22. Hagemeier C., Walker S., Caswell R., Kouzarides T., Sinclair J. The human cytomegalovirus 80-kilodalton but not the 72-kilodalton immediate-early protein transactivates heterologous promoters in a TATA box-dependent mechanism and interacts directly with TFIID. J Virol. 1992 Jul;66(7):4452–4456. doi: 10.1128/jvi.66.7.4452-4456.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hardwicke M. A., Vaughan P. J., Sekulovich R. E., O'Conner R., Sandri-Goldin R. M. The regions important for the activator and repressor functions of herpes simplex virus type 1 alpha protein ICP27 map to the C-terminal half of the molecule. J Virol. 1989 Nov;63(11):4590–4602. doi: 10.1128/jvi.63.11.4590-4602.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. 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]
  25. Hutchinson N. I., Sondermeyer R. T., Tocci M. J. Organization and expression of the major genes from the long inverted repeat of the human cytomegalovirus genome. Virology. 1986 Nov;155(1):160–171. doi: 10.1016/0042-6822(86)90176-5. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Kenney S., Kamine J., Holley-Guthrie E., Mar E. C., Lin J. C., Markovitz D., Pagano J. The Epstein-Barr virus immediate-early gene product, BMLF1, acts in trans by a posttranscriptional mechanism which is reporter gene dependent. J Virol. 1989 Sep;63(9):3870–3877. doi: 10.1128/jvi.63.9.3870-3877.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Kouzarides T., Bankier A. T., Satchwell S. C., Preddy E., Barrell B. G. An immediate early gene of human cytomegalovirus encodes a potential membrane glycoprotein. Virology. 1988 Jul;165(1):151–164. doi: 10.1016/0042-6822(88)90668-x. [DOI] [PubMed] [Google Scholar]
  29. Lang D., Fickenscher H., Stamminger T. Analysis of proteins binding to the proximal promoter region of the human cytomegalovirus IE-1/2 enhancer/promoter reveals both consensus and aberrant recognition sequences for transcription factors Sp1 and CREB. Nucleic Acids Res. 1992 Jul 11;20(13):3287–3295. doi: 10.1093/nar/20.13.3287. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. 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]
  31. Lieberman P. M., O'Hare P., Hayward G. S., Hayward S. D. Promiscuous trans activation of gene expression by an Epstein-Barr virus-encoded early nuclear protein. J Virol. 1986 Oct;60(1):140–148. doi: 10.1128/jvi.60.1.140-148.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. MCGAVRAN M. H., SMITH M. G. ULTRASTRUCTURAL, CYTOCHEMICAL, AND MICROCHEMICAL OBSERVATIONS ON CYTOMEGALOVIRUS (SALIVARY GLAND VIRUS) INFECTION OF HUMAN CELLS IN TISSUE CULTURE. Exp Mol Pathol. 1965 Feb;76:1–10. doi: 10.1016/0014-4800(65)90019-5. [DOI] [PubMed] [Google Scholar]
  33. Malone C. L., Vesole D. H., Stinski M. F. Transactivation of a human cytomegalovirus early promoter by gene products from the immediate-early gene IE2 and augmentation by IE1: mutational analysis of the viral proteins. J Virol. 1990 Apr;64(4):1498–1506. doi: 10.1128/jvi.64.4.1498-1506.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. 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]
  35. McDonough S. H., Spector D. H. Transcription in human fibroblasts permissively infected by human cytomegalovirus strain AD169. Virology. 1983 Feb;125(1):31–46. doi: 10.1016/0042-6822(83)90061-2. [DOI] [PubMed] [Google Scholar]
  36. McDonough S. H., Staprans S. I., Spector D. H. Analysis of the major transcripts encoded by the long repeat of human cytomegalovirus strain AD169. J Virol. 1985 Mar;53(3):711–718. doi: 10.1128/jvi.53.3.711-718.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. McGeoch D. J., Cunningham C., McIntyre G., Dolan A. Comparative sequence analysis of the long repeat regions and adjoining parts of the long unique regions in the genomes of herpes simplex viruses types 1 and 2. J Gen Virol. 1991 Dec;72(Pt 12):3057–3075. doi: 10.1099/0022-1317-72-12-3057. [DOI] [PubMed] [Google Scholar]
  38. McLauchlan J., Phelan A., Loney C., Sandri-Goldin R. M., Clements J. B. Herpes simplex virus IE63 acts at the posttranscriptional level to stimulate viral mRNA 3' processing. J Virol. 1992 Dec;66(12):6939–6945. doi: 10.1128/jvi.66.12.6939-6945.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. McMahan L., Schaffer P. A. The repressing and enhancing functions of the herpes simplex virus regulatory protein ICP27 map to C-terminal regions and are required to modulate viral gene expression very early in infection. J Virol. 1990 Jul;64(7):3471–3485. doi: 10.1128/jvi.64.7.3471-3485.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Nicholas J., Cameron K. R., Coleman H., Newman C., Honess R. W. Analysis of nucleotide sequence of the rightmost 43 kbp of herpesvirus saimiri (HVS) L-DNA: general conservation of genetic organization between HVS and Epstein-Barr virus. Virology. 1992 May;188(1):296–310. doi: 10.1016/0042-6822(92)90759-i. [DOI] [PubMed] [Google Scholar]
  41. Nicholas J., Coles L. S., Newman C., Honess R. W. Regulation of the herpesvirus saimiri (HVS) delayed-early 110-kilodalton promoter by HVS immediate-early gene products and a homolog of the Epstein-Barr virus R trans activator. J Virol. 1991 May;65(5):2457–2466. doi: 10.1128/jvi.65.5.2457-2466.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Nicholas J., Gompels U. A., Craxton M. A., Honess R. W. Conservation of sequence and function between the product of the 52-kilodalton immediate-early gene of herpesvirus saimiri and the BMLF1-encoded transcriptional effector (EB2) of Epstein-Barr virus. J Virol. 1988 Sep;62(9):3250–3257. doi: 10.1128/jvi.62.9.3250-3257.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. 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]
  44. 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]
  45. Puchtler E., Stamminger T. An inducible promoter mediates abundant expression from the immediate-early 2 gene region of human cytomegalovirus at late times after infection. J Virol. 1991 Nov;65(11):6301–6306. doi: 10.1128/jvi.65.11.6301-6306.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. ROWE W. P., HARTLEY J. W., WATERMAN S., TURNER H. C., HUEBNER R. J. Cytopathogenic agent resembling human salivary gland virus recovered from tissue cultures of human adenoids. Proc Soc Exp Biol Med. 1956 Jun;92(2):418–424. [PubMed] [Google Scholar]
  47. Rice S. A., Knipe D. M. Gene-specific transactivation by herpes simplex virus type 1 alpha protein ICP27. J Virol. 1988 Oct;62(10):3814–3823. doi: 10.1128/jvi.62.10.3814-3823.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Rice S. A., Lam V., Knipe D. M. The acidic amino-terminal region of herpes simplex virus type 1 alpha protein ICP27 is required for an essential lytic function. J Virol. 1993 Apr;67(4):1778–1787. doi: 10.1128/jvi.67.4.1778-1787.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Rice S. A., Su L. S., Knipe D. M. Herpes simplex virus alpha protein ICP27 possesses separable positive and negative regulatory activities. J Virol. 1989 Aug;63(8):3399–3407. doi: 10.1128/jvi.63.8.3399-3407.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Rudolph S. A., Stamminger T., Jahn G. Transcriptional analysis of the eight-kilobase mRNA encoding the major capsid protein of human cytomegalovirus. J Virol. 1990 Oct;64(10):5167–5172. doi: 10.1128/jvi.64.10.5167-5172.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Sacks W. R., Greene C. C., Aschman D. P., Schaffer P. A. Herpes simplex virus type 1 ICP27 is an essential regulatory protein. J Virol. 1985 Sep;55(3):796–805. doi: 10.1128/jvi.55.3.796-805.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Sandri-Goldin R. M., Mendoza G. E. A herpesvirus regulatory protein appears to act post-transcriptionally by affecting mRNA processing. Genes Dev. 1992 May;6(5):848–863. doi: 10.1101/gad.6.5.848. [DOI] [PubMed] [Google Scholar]
  53. Sekulovich R. E., Leary K., Sandri-Goldin R. M. The herpes simplex virus type 1 alpha protein ICP27 can act as a trans-repressor or a trans-activator in combination with ICP4 and ICP0. J Virol. 1988 Dec;62(12):4510–4522. doi: 10.1128/jvi.62.12.4510-4522.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Sheets M. D., Ogg S. C., Wickens M. P. Point mutations in AAUAAA and the poly (A) addition site: effects on the accuracy and efficiency of cleavage and polyadenylation in vitro. Nucleic Acids Res. 1990 Oct 11;18(19):5799–5805. doi: 10.1093/nar/18.19.5799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Smith I. L., Hardwicke M. A., Sandri-Goldin R. M. Evidence that the herpes simplex virus immediate early protein ICP27 acts post-transcriptionally during infection to regulate gene expression. Virology. 1992 Jan;186(1):74–86. doi: 10.1016/0042-6822(92)90062-t. [DOI] [PubMed] [Google Scholar]
  56. Smith R. H., Zhao Y., O'Callaghan D. J. The equine herpesvirus 1 (EHV-1) UL3 gene, an ICP27 homolog, is necessary for full activation of gene expression directed by an EHV-1 late promoter. J Virol. 1993 Feb;67(2):1105–1109. doi: 10.1128/jvi.67.2.1105-1109.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Spector D. H., Klucher K. M., Rabert D. K., Wright D. A. Human cytomegalovirus early gene expression. Curr Top Microbiol Immunol. 1990;154:21–45. doi: 10.1007/978-3-642-74980-3_2. [DOI] [PubMed] [Google Scholar]
  58. 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]
  59. Stamminger T., Puchtler E., Fleckenstein B. Discordant expression of the immediate-early 1 and 2 gene regions of human cytomegalovirus at early times after infection involves posttranscriptional processing events. J Virol. 1991 May;65(5):2273–2282. doi: 10.1128/jvi.65.5.2273-2282.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Staprans S. I., Rabert D. K., Spector D. H. Identification of sequence requirements and trans-acting functions necessary for regulated expression of a human cytomegalovirus early gene. J Virol. 1988 Sep;62(9):3463–3473. doi: 10.1128/jvi.62.9.3463-3473.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Staprans S. I., Spector D. H. 2.2-kilobase class of early transcripts encoded by cell-related sequences in human cytomegalovirus strain AD169. J Virol. 1986 Feb;57(2):591–602. doi: 10.1128/jvi.57.2.591-602.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Stasiak P. C., Mocarski E. S. Transactivation of the cytomegalovirus ICP36 gene promoter requires the alpha gene product TRS1 in addition to IE1 and IE2. J Virol. 1992 Feb;66(2):1050–1058. doi: 10.1128/jvi.66.2.1050-1058.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Stenberg R. M., Depto A. S., Fortney J., Nelson J. A. Regulated expression of early and late RNAs and proteins from the human cytomegalovirus immediate-early gene region. J Virol. 1989 Jun;63(6):2699–2708. doi: 10.1128/jvi.63.6.2699-2708.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. 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]
  65. 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]
  66. Stenberg R. M., Witte P. R., Stinski M. F. Multiple spliced and unspliced transcripts from human cytomegalovirus immediate-early region 2 and evidence for a common initiation site within immediate-early region 1. J Virol. 1985 Dec;56(3):665–675. doi: 10.1128/jvi.56.3.665-675.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Su L., Knipe D. M. Herpes simplex virus alpha protein ICP27 can inhibit or augment viral gene transactivation. Virology. 1989 Jun;170(2):496–504. doi: 10.1016/0042-6822(89)90441-8. [DOI] [PubMed] [Google Scholar]
  68. 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]
  69. 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]
  70. 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]
  71. Wathen M. W., Thomsen D. R., Stinski M. F. Temporal regulation of human cytomegalovirus transcription at immediate early and early times after infection. J Virol. 1981 May;38(2):446–459. doi: 10.1128/jvi.38.2.446-459.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Welch A. R., McNally L. M., Gibson W. Cytomegalovirus assembly protein nested gene family: four 3'-coterminal transcripts encode four in-frame, overlapping proteins. J Virol. 1991 Aug;65(8):4091–4100. doi: 10.1128/jvi.65.8.4091-4100.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Weston K. An enhancer element in the short unique region of human cytomegalovirus regulates the production of a group of abundant immediate early transcripts. Virology. 1988 Feb;162(2):406–416. doi: 10.1016/0042-6822(88)90481-3. [DOI] [PubMed] [Google Scholar]
  74. Wilcox K. W., Kohn A., Sklyanskaya E., Roizman B. Herpes simplex virus phosphoproteins. I. Phosphate cycles on and off some viral polypeptides and can alter their affinity for DNA. J Virol. 1980 Jan;33(1):167–182. doi: 10.1128/jvi.33.1.167-182.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  75. Wong K. M., Levine A. J. Characterization of proteins encoded by the Epstein-Barr virus transactivator gene BMLF1. Virology. 1989 Jan;168(1):101–111. doi: 10.1016/0042-6822(89)90408-x. [DOI] [PubMed] [Google Scholar]
  76. Wong K. M., Levine A. J. Identification and mapping of Epstein-Barr virus early antigens and demonstration of a viral gene activator that functions in trans. J Virol. 1986 Oct;60(1):149–156. doi: 10.1128/jvi.60.1.149-156.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. de Wet J. R., Wood K. V., DeLuca M., Helinski D. R., Subramani S. Firefly luciferase gene: structure and expression in mammalian cells. Mol Cell Biol. 1987 Feb;7(2):725–737. doi: 10.1128/mcb.7.2.725. [DOI] [PMC free article] [PubMed] [Google Scholar]

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