Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1996 Dec;70(12):8691–8700. doi: 10.1128/jvi.70.12.8691-8700.1996

Human cytomegalovirus mtrII oncoprotein binds to p53 and down-regulates p53-activated transcription.

S Muralidhar 1, J Doniger 1, E Mendelson 1, J C Araujo 1, F Kashanchi 1, N Azumi 1, J N Brady 1, L J Rosenthal 1
PMCID: PMC190964  PMID: 8970996

Abstract

The 79-amino-acid (79-aa) open reading frame (UL111a) gene within morphological transforming region II (mtrII) of human cytomegalovirus strain Towne has been shown to transform rodent cells in vitro (J. Thompson, J. Doniger, and L. J. Rosenthal, Arch. Virol. 136:161-172, 1994). Moreover, a translation termination linker (TTL) mutant of mtrII that coded for the first 49 aa of mtrII oncoprotein (designated TTL49) was sufficient for malignant transformation, whereas a TTL mutant that coded for the first 24 aa (designated TTL24) was not. The current study demonstrates the binding of mtrII oncoprotein to the tumor suppressor protein p53 both in vivo using transiently transfected cells and in vitro using labeled proteins. Furthermore, the C-terminally truncated mtrII protein TTL49, but not truncated protein TTL24, bound to p53. The mtrII binding domain mapped to the N-terminal region of p53, residues 1 to 106, with a critical region from aa 27 to 44, whereas the p53 binding domain of mtrII protein was the first 49 aa. Furthermore, mtrII inhibited p53-activated transcription, indicating its ability to alter p53-directed cellular regulatory mechanisms. mtrII oncoprotein was detected both in stably transfected NIH 3T3 cell lines and human cytomegalovirus-infected HEL 299 cells (as early as 12 h after infection) in the perinuclear region and in the nucleus. mtrII-transformed cell lines, at both early and late passage, exhibited high levels of p53 with a 15-fold-extended half-life. However, p53-activated transcription was suppressed in these cells in spite of the increased p53 levels. Finally, the results with wild-type mtrII and its TTL mutants with respect to p53 binding, p53-activated transcription, and transforming ability suggest that the mechanism of mtrII transformation is linked to both p53 binding and disruption of p53 cell regulation.

Full Text

The Full Text of this article is available as a PDF (614.5 KB).

Selected References

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

  1. Albrecht T., Rapp F. Malignant transformation of hamster embryo fibroblasts following exposure to ultraviolet-irradiated human cytomegalovirus. Virology. 1973 Sep;55(1):53–61. doi: 10.1016/s0042-6822(73)81007-4. [DOI] [PubMed] [Google Scholar]
  2. Azumi N., Traweek S. T., Battifora H. Prostatic acid phosphatase in carcinoid tumors. Immunohistochemical and immunoblot studies. Am J Surg Pathol. 1991 Aug;15(8):785–790. doi: 10.1097/00000478-199108000-00009. [DOI] [PubMed] [Google Scholar]
  3. Barak Y., Juven T., Haffner R., Oren M. mdm2 expression is induced by wild type p53 activity. EMBO J. 1993 Feb;12(2):461–468. doi: 10.1002/j.1460-2075.1993.tb05678.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Boldogh I., AbuBakar S., Albrecht T. Activation of proto-oncogenes: an immediate early event in human cytomegalovirus infection. Science. 1990 Feb 2;247(4942):561–564. doi: 10.1126/science.1689075. [DOI] [PubMed] [Google Scholar]
  5. Boldogh I., AbuBakar S., Deng C. Z., Albrecht T. Transcriptional activation of cellular oncogenes fos, jun, and myc by human cytomegalovirus. J Virol. 1991 Mar;65(3):1568–1571. doi: 10.1128/jvi.65.3.1568-1571.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chen C. Y., Oliner J. D., Zhan Q., Fornace A. J., Jr, Vogelstein B., Kastan M. B. Interactions between p53 and MDM2 in a mammalian cell cycle checkpoint pathway. Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2684–2688. doi: 10.1073/pnas.91.7.2684. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Clanton D. J., Jariwalla R. J., Kress C., Rosenthal L. J. Neoplastic transformation by a cloned human cytomegalovirus DNA fragment uniquely homologous to one of the transforming regions of herpes simplex virus type 2. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3826–3830. doi: 10.1073/pnas.80.12.3826. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Crook T., Marston N. J., Sara E. A., Vousden K. H. Transcriptional activation by p53 correlates with suppression of growth but not transformation. Cell. 1994 Dec 2;79(5):817–827. doi: 10.1016/0092-8674(94)90071-x. [DOI] [PubMed] [Google Scholar]
  9. Dutta A., Ruppert J. M., Aster J. C., Winchester E. Inhibition of DNA replication factor RPA by p53. Nature. 1993 Sep 2;365(6441):79–82. doi: 10.1038/365079a0. [DOI] [PubMed] [Google Scholar]
  10. Dyson N., Howley P. M., Münger K., Harlow E. The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. Science. 1989 Feb 17;243(4893):934–937. doi: 10.1126/science.2537532. [DOI] [PubMed] [Google Scholar]
  11. Ensoli B., Lusso P., Schachter F., Josephs S. F., Rappaport J., Negro F., Gallo R. C., Wong-Staal F. Human herpes virus-6 increases HIV-1 expression in co-infected T cells via nuclear factors binding to the HIV-1 enhancer. EMBO J. 1989 Oct;8(10):3019–3027. doi: 10.1002/j.1460-2075.1989.tb08452.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Finlay C. A., Hinds P. W., Tan T. H., Eliyahu D., Oren M., Levine A. J. Activating mutations for transformation by p53 produce a gene product that forms an hsc70-p53 complex with an altered half-life. Mol Cell Biol. 1988 Feb;8(2):531–539. doi: 10.1128/mcb.8.2.531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Foster S. A., Demers G. W., Etscheid B. G., Galloway D. A. The ability of human papillomavirus E6 proteins to target p53 for degradation in vivo correlates with their ability to abrogate actinomycin D-induced growth arrest. J Virol. 1994 Sep;68(9):5698–5705. doi: 10.1128/jvi.68.9.5698-5705.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Galloway D. A., Nelson J. A., McDougall J. K. Small fragments of herpesvirus DNA with transforming activity contain insertion sequence-like structures. Proc Natl Acad Sci U S A. 1984 Aug;81(15):4736–4740. doi: 10.1073/pnas.81.15.4736. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ginsberg D., Mechta F., Yaniv M., Oren M. Wild-type p53 can down-modulate the activity of various promoters. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):9979–9983. doi: 10.1073/pnas.88.22.9979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gitlin S. D., Dittmer J., Shin R. C., Brady J. N. Transcriptional activation of the human T-lymphotropic virus type I long terminal repeat by functional interaction of Tax1 and Ets1. J Virol. 1993 Dec;67(12):7307–7316. doi: 10.1128/jvi.67.12.7307-7316.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hollstein M., Sidransky D., Vogelstein B., Harris C. C. p53 mutations in human cancers. Science. 1991 Jul 5;253(5015):49–53. doi: 10.1126/science.1905840. [DOI] [PubMed] [Google Scholar]
  18. Inamdar A., Thompson J., Kashanchi F., Doniger J., Brady J. N., Rosenthal L. J. Identification of two promoters within human cytomegalovirus morphologic transforming region II. Intervirology. 1992;34(3):146–153. doi: 10.1159/000150275. [DOI] [PubMed] [Google Scholar]
  19. Jahan N., Razzaque A., Brady J., Rosenthal L. J. The human cytomegalovirus mtrII colinear region in strain Tanaka is transformation defective. J Virol. 1989 Jun;63(6):2866–2869. doi: 10.1128/jvi.63.6.2866-2869.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Jariwalla R. J., Razzaque A., Lawson S., Rosenthal L. J. Tumor progression mediated by two cooperating DNA segments of human cytomegalovirus. J Virol. 1989 Jan;63(1):425–428. doi: 10.1128/jvi.63.1.425-428.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kao C. C., Yew P. R., Berk A. J. Domains required for in vitro association between the cellular p53 and the adenovirus 2 E1B 55K proteins. Virology. 1990 Dec;179(2):806–814. doi: 10.1016/0042-6822(90)90148-k. [DOI] [PubMed] [Google Scholar]
  22. Kashanchi F., Duvall J. F., Brady J. N. Electroporation of viral transactivator proteins into lymphocyte suspension cells. Nucleic Acids Res. 1992 Sep 11;20(17):4673–4674. doi: 10.1093/nar/20.17.4673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kastan M. B., Zhan Q., el-Deiry W. S., Carrier F., Jacks T., Walsh W. V., Plunkett B. S., Vogelstein B., Fornace A. J., Jr A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia. Cell. 1992 Nov 13;71(4):587–597. doi: 10.1016/0092-8674(92)90593-2. [DOI] [PubMed] [Google Scholar]
  24. Kuerbitz S. J., Plunkett B. S., Walsh W. V., Kastan M. B. Wild-type p53 is a cell cycle checkpoint determinant following irradiation. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7491–7495. doi: 10.1073/pnas.89.16.7491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lane D. P., Crawford L. V. T antigen is bound to a host protein in SV40-transformed cells. Nature. 1979 Mar 15;278(5701):261–263. doi: 10.1038/278261a0. [DOI] [PubMed] [Google Scholar]
  26. Lin J., Chen J., Elenbaas B., Levine A. J. Several hydrophobic amino acids in the p53 amino-terminal domain are required for transcriptional activation, binding to mdm-2 and the adenovirus 5 E1B 55-kD protein. Genes Dev. 1994 May 15;8(10):1235–1246. doi: 10.1101/gad.8.10.1235. [DOI] [PubMed] [Google Scholar]
  27. Liu X., Miller C. W., Koeffler P. H., Berk A. J. The p53 activation domain binds the TATA box-binding polypeptide in Holo-TFIID, and a neighboring p53 domain inhibits transcription. Mol Cell Biol. 1993 Jun;13(6):3291–3300. doi: 10.1128/mcb.13.6.3291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Lo S. K., Ip K. W., Chan P. K., Nicholls J. M., Heath R. B., Shiu S. Y. Congenital infection by human cytomegalovirus with a 65bp deletion in the morphological transforming region II. Arch Virol. 1993;129(1-4):295–299. doi: 10.1007/BF01316904. [DOI] [PubMed] [Google Scholar]
  29. Lowe S. W., Schmitt E. M., Smith S. W., Osborne B. A., Jacks T. p53 is required for radiation-induced apoptosis in mouse thymocytes. Nature. 1993 Apr 29;362(6423):847–849. doi: 10.1038/362847a0. [DOI] [PubMed] [Google Scholar]
  30. Maheswaran S., Englert C., Bennett P., Heinrich G., Haber D. A. The WT1 gene product stabilizes p53 and inhibits p53-mediated apoptosis. Genes Dev. 1995 Sep 1;9(17):2143–2156. doi: 10.1101/gad.9.17.2143. [DOI] [PubMed] [Google Scholar]
  31. Malkin D., Li F. P., Strong L. C., Fraumeni J. F., Jr, Nelson C. E., Kim D. H., Kassel J., Gryka M. A., Bischoff F. Z., Tainsky M. A. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science. 1990 Nov 30;250(4985):1233–1238. doi: 10.1126/science.1978757. [DOI] [PubMed] [Google Scholar]
  32. Mansur C. P., Marcus B., Dalal S., Androphy E. J. The domain of p53 required for binding HPV 16 E6 is separable from the degradation domain. Oncogene. 1995 Feb 2;10(3):457–465. [PubMed] [Google Scholar]
  33. Midgley C. A., Fisher C. J., Bártek J., Vojtesek B., Lane D., Barnes D. M. Analysis of p53 expression in human tumours: an antibody raised against human p53 expressed in Escherichia coli. J Cell Sci. 1992 Jan;101(Pt 1):183–189. doi: 10.1242/jcs.101.1.183. [DOI] [PubMed] [Google Scholar]
  34. Mietz J. A., Unger T., Huibregtse J. M., Howley P. M. The transcriptional transactivation function of wild-type p53 is inhibited by SV40 large T-antigen and by HPV-16 E6 oncoprotein. EMBO J. 1992 Dec;11(13):5013–5020. doi: 10.1002/j.1460-2075.1992.tb05608.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Miyashita T., Reed J. C. Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell. 1995 Jan 27;80(2):293–299. doi: 10.1016/0092-8674(95)90412-3. [DOI] [PubMed] [Google Scholar]
  36. Muganda P., Mendoza O., Hernandez J., Qian Q. Human cytomegalovirus elevates levels of the cellular protein p53 in infected fibroblasts. J Virol. 1994 Dec;68(12):8028–8034. doi: 10.1128/jvi.68.12.8028-8034.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Nelson J. A., Fleckenstein B., Jahn G., Galloway D. A., McDougall J. K. Structure of the transforming region of human cytomegalovirus AD169. J Virol. 1984 Jan;49(1):109–115. doi: 10.1128/jvi.49.1.109-115.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Nissim A., Hoogenboom H. R., Tomlinson I. M., Flynn G., Midgley C., Lane D., Winter G. Antibody fragments from a 'single pot' phage display library as immunochemical reagents. EMBO J. 1994 Feb 1;13(3):692–698. doi: 10.1002/j.1460-2075.1994.tb06308.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Oliner J. D., Pietenpol J. A., Thiagalingam S., Gyuris J., Kinzler K. W., Vogelstein B. Oncoprotein MDM2 conceals the activation domain of tumour suppressor p53. Nature. 1993 Apr 29;362(6423):857–860. doi: 10.1038/362857a0. [DOI] [PubMed] [Google Scholar]
  40. Oren M., Maltzman W., Levine A. J. Post-translational regulation of the 54K cellular tumor antigen in normal and transformed cells. Mol Cell Biol. 1981 Feb;1(2):101–110. doi: 10.1128/mcb.1.2.101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Ragimov N., Krauskopf A., Navot N., Rotter V., Oren M., Aloni Y. Wild-type but not mutant p53 can repress transcription initiation in vitro by interfering with the binding of basal transcription factors to the TATA motif. Oncogene. 1993 May;8(5):1183–1193. [PubMed] [Google Scholar]
  42. Ramirez M. L., Virmani M., Garon C., Rosenthal L. J. Defective virions of human cytomegalovirus. Virology. 1979 Jul 15;96(1):311–314. doi: 10.1016/0042-6822(79)90201-0. [DOI] [PubMed] [Google Scholar]
  43. Razzaque A., Jahan N., McWeeney D., Jariwalla R. J., Jones C., Brady J., Rosenthal L. J. Localization and DNA sequence analysis of the transforming domain (mtrII) of human cytomegalovirus. Proc Natl Acad Sci U S A. 1988 Aug;85(15):5709–5713. doi: 10.1073/pnas.85.15.5709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Reich N. C., Levine A. J. Growth regulation of a cellular tumour antigen, p53, in nontransformed cells. Nature. 1984 Mar 8;308(5955):199–201. doi: 10.1038/308199a0. [DOI] [PubMed] [Google Scholar]
  45. Reid R. L., Lindholm P. F., Mireskandari A., Dittmer J., Brady J. N. Stabilization of wild-type p53 in human T-lymphocytes transformed by HTLV-I. Oncogene. 1993 Nov;8(11):3029–3036. [PubMed] [Google Scholar]
  46. Rogel A., Popliker M., Webb C. G., Oren M. p53 cellular tumor antigen: analysis of mRNA levels in normal adult tissues, embryos, and tumors. Mol Cell Biol. 1985 Oct;5(10):2851–2855. doi: 10.1128/mcb.5.10.2851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Ruppert J. M., Stillman B. Analysis of a protein-binding domain of p53. Mol Cell Biol. 1993 Jun;13(6):3811–3820. doi: 10.1128/mcb.13.6.3811. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Sarnow P., Ho Y. S., Williams J., Levine A. J. Adenovirus E1b-58kd tumor antigen and SV40 large tumor antigen are physically associated with the same 54 kd cellular protein in transformed cells. Cell. 1982 Feb;28(2):387–394. doi: 10.1016/0092-8674(82)90356-7. [DOI] [PubMed] [Google Scholar]
  49. Scheffner M., Werness B. A., Huibregtse J. M., Levine A. J., Howley P. M. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell. 1990 Dec 21;63(6):1129–1136. doi: 10.1016/0092-8674(90)90409-8. [DOI] [PubMed] [Google Scholar]
  50. Schreier A. A., Gruber J. Viral T-antigen interactions with cellular proto-oncogene and anti-oncogene products. J Natl Cancer Inst. 1990 Mar 7;82(5):354–360. doi: 10.1093/jnci/82.5.354. [DOI] [PubMed] [Google Scholar]
  51. Seto E., Usheva A., Zambetti G. P., Momand J., Horikoshi N., Weinmann R., Levine A. J., Shenk T. Wild-type p53 binds to the TATA-binding protein and represses transcription. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12028–12032. doi: 10.1073/pnas.89.24.12028. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Smith M. L., Chen I. T., Zhan Q., Bae I., Chen C. Y., Gilmer T. M., Kastan M. B., O'Connor P. M., Fornace A. J., Jr Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen. Science. 1994 Nov 25;266(5189):1376–1380. doi: 10.1126/science.7973727. [DOI] [PubMed] [Google Scholar]
  53. Soussi T., Caron de Fromentel C., May P. Structural aspects of the p53 protein in relation to gene evolution. Oncogene. 1990 Jul;5(7):945–952. [PubMed] [Google Scholar]
  54. Speir E., Modali R., Huang E. S., Leon M. B., Shawl F., Finkel T., Epstein S. E. Potential role of human cytomegalovirus and p53 interaction in coronary restenosis. Science. 1994 Jul 15;265(5170):391–394. doi: 10.1126/science.8023160. [DOI] [PubMed] [Google Scholar]
  55. Subler M. A., Martin D. W., Deb S. Inhibition of viral and cellular promoters by human wild-type p53. J Virol. 1992 Aug;66(8):4757–4762. doi: 10.1128/jvi.66.8.4757-4762.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Thompson J., Doniger J., Rosenthal L. J. A 79 amino acid oncogene is responsible for human cytomegalovirus mtrII induced malignant transformation. Arch Virol. 1994;136(1-2):161–172. doi: 10.1007/BF01538825. [DOI] [PubMed] [Google Scholar]
  57. Thompson J., Inamdar A., Jahan N., Doniger J., Rosenthal L. J. Localization and sequence analysis of morphological transforming region III within human cytomegalovirus strain Towne. Intervirology. 1993;36(3):121–127. doi: 10.1159/000150330. [DOI] [PubMed] [Google Scholar]
  58. Truant R., Xiao H., Ingles C. J., Greenblatt J. Direct interaction between the transcriptional activation domain of human p53 and the TATA box-binding protein. J Biol Chem. 1993 Feb 5;268(4):2284–2287. [PubMed] [Google Scholar]
  59. Ueda H., Ullrich S. J., Gangemi J. D., Kappel C. A., Ngo L., Feitelson M. A., Jay G. Functional inactivation but not structural mutation of p53 causes liver cancer. Nat Genet. 1995 Jan;9(1):41–47. doi: 10.1038/ng0195-41. [DOI] [PubMed] [Google Scholar]
  60. Wang P., Reed M., Wang Y., Mayr G., Stenger J. E., Anderson M. E., Schwedes J. F., Tegtmeyer P. p53 domains: structure, oligomerization, and transformation. Mol Cell Biol. 1994 Aug;14(8):5182–5191. doi: 10.1128/mcb.14.8.5182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Wang S. F., Zhao Y., Fu Q. L., Yin M. B., Liu Y. Y. [Detection of cytomegalovirus (CMV) DNA sequence in biopsy samples of cervical cancer]. Zhonghua Zhong Liu Za Zhi. 1987 Jul;9(4):279–281. [PubMed] [Google Scholar]
  62. Wang X. W., Forrester K., Yeh H., Feitelson M. A., Gu J. R., Harris C. C. Hepatitis B virus X protein inhibits p53 sequence-specific DNA binding, transcriptional activity, and association with transcription factor ERCC3. Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2230–2234. doi: 10.1073/pnas.91.6.2230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Wang Y., Reed M., Wang P., Stenger J. E., Mayr G., Anderson M. E., Schwedes J. F., Tegtmeyer P. p53 domains: identification and characterization of two autonomous DNA-binding regions. Genes Dev. 1993 Dec;7(12B):2575–2586. doi: 10.1101/gad.7.12b.2575. [DOI] [PubMed] [Google Scholar]
  64. Werness B. A., Levine A. J., Howley P. M. Association of human papillomavirus types 16 and 18 E6 proteins with p53. Science. 1990 Apr 6;248(4951):76–79. doi: 10.1126/science.2157286. [DOI] [PubMed] [Google Scholar]
  65. Whyte P., Buchkovich K. J., Horowitz J. M., Friend S. H., Raybuck M., Weinberg R. A., Harlow E. Association between an oncogene and an anti-oncogene: the adenovirus E1A proteins bind to the retinoblastoma gene product. Nature. 1988 Jul 14;334(6178):124–129. doi: 10.1038/334124a0. [DOI] [PubMed] [Google Scholar]
  66. Yew P. R., Berk A. J. Inhibition of p53 transactivation required for transformation by adenovirus early 1B protein. Nature. 1992 May 7;357(6373):82–85. doi: 10.1038/357082a0. [DOI] [PubMed] [Google Scholar]
  67. Yew P. R., Liu X., Berk A. J. Adenovirus E1B oncoprotein tethers a transcriptional repression domain to p53. Genes Dev. 1994 Jan;8(2):190–202. doi: 10.1101/gad.8.2.190. [DOI] [PubMed] [Google Scholar]
  68. Zantema A., Fransen J. A., Davis-Olivier A., Ramaekers F. C., Vooijs G. P., DeLeys B., Van der Eb A. J. Localization of the E1B proteins of adenovirus 5 in transformed cells, as revealed by interaction with monoclonal antibodies. Virology. 1985 Apr 15;142(1):44–58. doi: 10.1016/0042-6822(85)90421-0. [DOI] [PubMed] [Google Scholar]
  69. el-Beik T., Razzaque A., Jariwalla R., Cihlar R. L., Rosenthal L. J. Multiple transforming regions of human cytomegalovirus DNA. J Virol. 1986 Nov;60(2):645–652. doi: 10.1128/jvi.60.2.645-652.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. el-Deiry W. S., Tokino T., Velculescu V. E., Levy D. B., Parsons R., Trent J. M., Lin D., Mercer W. E., Kinzler K. W., Vogelstein B. WAF1, a potential mediator of p53 tumor suppression. Cell. 1993 Nov 19;75(4):817–825. doi: 10.1016/0092-8674(93)90500-p. [DOI] [PubMed] [Google Scholar]
  71. zur Hausen H. Viruses in human cancers. Science. 1991 Nov 22;254(5035):1167–1173. doi: 10.1126/science.1659743. [DOI] [PubMed] [Google Scholar]

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

RESOURCES