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. 1995 Dec;69(12):7639–7647. doi: 10.1128/jvi.69.12.7639-7647.1995

Oncogenicity of human papillomavirus- or adenovirus-transformed cells correlates with resistance to lysis by natural killer cells.

J M Routes 1, S Ryan 1
PMCID: PMC189704  PMID: 7494272

Abstract

The reasons for the dissimilar oncogenicities of human adenoviruses and human papillomaviruses (HPV) in humans are unknown but may relate to differences in the capacities of the E1A and E7 proteins to target cells for rejection by the host natural killer (NK) cell response. As one test of this hypothesis, we compared the abilities of E1A- and E7-expressing human fibroblastic or keratinocyte-derived human cells to be selectively killed by either unstimulated or interferon (IFN)-activated NK cells. Cells expressing the E1A oncoprotein were selectively killed by unstimulated NK cells, while the same parental cells but expressing the HPV type 16 (HPV-16) or HPV-18 E7 oncoprotein were resistant to NK cell lysis. The ability of IFN-activated NK cells to selectively kill virally transformed cells depends on IFN's ability to induce resistance to NK cell lysis in normal (i.e., non-viral oncogene-expressing) but not virally transformed cells. E1A blocked IFN's induction of cytolytic resistance, resulting in the selective lysis of adenovirus-transformed cells by IFN-activated NK cells. The extent of IFN-induced NK cell killing of E1A-expressing cells was proportional to the level of E1A expression and correlated with the ability of E1A to block IFN-stimulated gene expression in target cells. In contrast, E7 blocked neither IFN-stimulated gene expression nor IFN's induction of cytolytic resistance, thereby precluding the selective lysis of HPV-transformed cells by IFN-activated NK cells. In conclusion, E1A expression marks cells for destruction by the host NK cell response, whereas the E7 oncoprotein lacks this activity.

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Selected References

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  1. Anderson K. P., Fennie E. H. Adenovirus early region 1A modulation of interferon antiviral activity. J Virol. 1987 Mar;61(3):787–795. doi: 10.1128/jvi.61.3.787-795.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baker C. C., Phelps W. C., Lindgren V., Braun M. J., Gonda M. A., Howley P. M. Structural and transcriptional analysis of human papillomavirus type 16 sequences in cervical carcinoma cell lines. J Virol. 1987 Apr;61(4):962–971. doi: 10.1128/jvi.61.4.962-971.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bergsagel D. J., Finegold M. J., Butel J. S., Kupsky W. J., Garcea R. L. DNA sequences similar to those of simian virus 40 in ependymomas and choroid plexus tumors of childhood. N Engl J Med. 1992 Apr 9;326(15):988–993. doi: 10.1056/NEJM199204093261504. [DOI] [PubMed] [Google Scholar]
  4. Brunet L. J., Berk A. J. Concentration dependence of transcriptional transactivation in inducible E1A-containing human cells. Mol Cell Biol. 1988 Nov;8(11):4799–4807. doi: 10.1128/mcb.8.11.4799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bukowski J. F., Welsh R. M. Inability of interferon to protect virus-infected cells against lysis by natural killer (NK) cells correlates with NK cell-mediated antiviral effects in vivo. J Immunol. 1985 Nov;135(5):3537–3541. [PubMed] [Google Scholar]
  6. Burgert H. G., Maryanski J. L., Kvist S. "E3/19K" protein of adenovirus type 2 inhibits lysis of cytolytic T lymphocytes by blocking cell-surface expression of histocompatibility class I antigens. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1356–1360. doi: 10.1073/pnas.84.5.1356. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Butel J. S., Tevethia S. S., Melnick J. L. Oncogenicity and cell transformation by papovavirus SV40: the role of the viral genome. Adv Cancer Res. 1972;15:1–55. doi: 10.1016/s0065-230x(08)60371-1. [DOI] [PubMed] [Google Scholar]
  8. Carbone M., Pass H. I., Rizzo P., Marinetti M., Di Muzio M., Mew D. J., Levine A. S., Procopio A. Simian virus 40-like DNA sequences in human pleural mesothelioma. Oncogene. 1994 Jun;9(6):1781–1790. [PubMed] [Google Scholar]
  9. Cook J. L., Hibbs J. B., Jr, Lewis A. M., Jr DNA virus-transformed hamster cell--host effector cell interactions: level of resistance to cytolysis correlated with tumorigenicity. Int J Cancer. 1982 Dec 15;30(6):795–803. doi: 10.1002/ijc.2910300619. [DOI] [PubMed] [Google Scholar]
  10. Cook J. L., Hibbs J. B., Jr, Lewis A. M., Jr Resistance of simian virus 40-transformed hamster cells to the cytolytic effect of activated macrophages: a possible factor in species-specific viral oncogenicity. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6773–6777. doi: 10.1073/pnas.77.11.6773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cook J. L., Lewis A. M., Jr Differential NK cell and macrophage killing of hamster cells infected with nononcogenic or oncogenic adenovirus. Science. 1984 May 11;224(4649):612–615. doi: 10.1126/science.6710160. [DOI] [PubMed] [Google Scholar]
  12. Cook J. L., Lewis A. M., Jr Immunological surveillance against DNA-virus-transformed cells: correlations between natural killer cell cytolytic competence and tumor susceptibility of athymic rodents. J Virol. 1987 Jul;61(7):2155–2161. doi: 10.1128/jvi.61.7.2155-2161.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Cook J. L., May D. L., Lewis A. M., Jr, Walker T. A. Adenovirus E1A gene induction of susceptibility to lysis by natural killer cells and activated macrophages in infected rodent cells. J Virol. 1987 Nov;61(11):3510–3520. doi: 10.1128/jvi.61.11.3510-3520.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Cook J. L., Walker T. A., Lewis A. M., Jr, Ruley H. E., Graham F. L., Pilder S. H. Expression of the adenovirus E1A oncogene during cell transformation is sufficient to induce susceptibility to lysis by host inflammatory cells. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6965–6969. doi: 10.1073/pnas.83.18.6965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Cook J. L., Wilson B. A., Wolf L. A., Walker T. A. E1A oncogene expression level in sarcoma cells: an independent determinant of cytolytic susceptibility and tumor rejection. Oncogene. 1993 Mar;8(3):625–635. [PubMed] [Google Scholar]
  16. Dyson N., Bernards R., Friend S. H., Gooding L. R., Hassell J. A., Major E. O., Pipas J. M., Vandyke T., Harlow E. Large T antigens of many polyomaviruses are able to form complexes with the retinoblastoma protein. J Virol. 1990 Mar;64(3):1353–1356. doi: 10.1128/jvi.64.3.1353-1356.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Dyson N., Buchkovich K., Whyte P., Harlow E. The cellular 107K protein that binds to adenovirus E1A also associates with the large T antigens of SV40 and JC virus. Cell. 1989 Jul 28;58(2):249–255. doi: 10.1016/0092-8674(89)90839-8. [DOI] [PubMed] [Google Scholar]
  18. Dyson N., Guida P., Münger K., Harlow E. Homologous sequences in adenovirus E1A and human papillomavirus E7 proteins mediate interaction with the same set of cellular proteins. J Virol. 1992 Dec;66(12):6893–6902. doi: 10.1128/jvi.66.12.6893-6902.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Dyson N., Harlow E. Adenovirus E1A targets key regulators of cell proliferation. Cancer Surv. 1992;12:161–195. [PubMed] [Google Scholar]
  20. Egan C., Jelsma T. N., Howe J. A., Bayley S. T., Ferguson B., Branton P. E. Mapping of cellular protein-binding sites on the products of early-region 1A of human adenovirus type 5. Mol Cell Biol. 1988 Sep;8(9):3955–3959. doi: 10.1128/mcb.8.9.3955. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ellis T. M., McKenzie R. S., Simms P. E., Helfrich B. A., Fisher R. I. Induction of human lymphokine-activated killer cells by IFN-alpha and IFN-gamma. J Immunol. 1989 Dec 15;143(12):4282–4286. [PubMed] [Google Scholar]
  22. Fresa K. L., Karjalainen H. E., Tevethia S. S. Sensitivity of simian virus 40-transformed C57BL/6 mouse embryo fibroblasts to lysis by murine natural killer cells. J Immunol. 1987 Feb 15;138(4):1215–1220. [PubMed] [Google Scholar]
  23. Frisch S. M. Antioncogenic effect of adenovirus E1A in human tumor cells. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9077–9081. doi: 10.1073/pnas.88.20.9077. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Furbert-Harris P. M., Evans C. H., Woodworth C. D., DiPaolo J. A. Loss of leukoregulin up-regulation of natural killer but not lymphokine-activated killer lymphocytotoxicity in human papillomavirus 16 DNA-immortalized cervical epithelial cells. J Natl Cancer Inst. 1989 Jul 19;81(14):1080–1085. doi: 10.1093/jnci/81.14.1080. [DOI] [PubMed] [Google Scholar]
  25. Gallimore P. H., Paraskeva C. A study to determine the reasons for differences in the tumorigenicity of rat cell lines transformed by adenovirus 2 and adenovirus 12. Cold Spring Harb Symp Quant Biol. 1980;44(Pt 1):703–713. doi: 10.1101/sqb.1980.044.01.075. [DOI] [PubMed] [Google Scholar]
  26. Gooding L. R., Aquino L., Duerksen-Hughes P. J., Day D., Horton T. M., Yei S. P., Wold W. S. The E1B 19,000-molecular-weight protein of group C adenoviruses prevents tumor necrosis factor cytolysis of human cells but not of mouse cells. J Virol. 1991 Jun;65(6):3083–3094. doi: 10.1128/jvi.65.6.3083-3094.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Gooding L. R., Elmore L. W., Tollefson A. E., Brady H. A., Wold W. S. A 14,700 MW protein from the E3 region of adenovirus inhibits cytolysis by tumor necrosis factor. Cell. 1988 May 6;53(3):341–346. doi: 10.1016/0092-8674(88)90154-7. [DOI] [PubMed] [Google Scholar]
  28. Green M., Wold W. S., Mackey J. K., Rigden P. Analysis of human tonsil and cancer DNAs and RNAs for DNA sequences of group C (serotypes 1, 2, 5, and 6) human adenoviruses. Proc Natl Acad Sci U S A. 1979 Dec;76(12):6606–6610. doi: 10.1073/pnas.76.12.6606. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Gutch M. J., Reich N. C. Repression of the interferon signal transduction pathway by the adenovirus E1A oncogene. Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):7913–7917. doi: 10.1073/pnas.88.18.7913. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Halbert C. L., Demers G. W., Galloway D. A. The E7 gene of human papillomavirus type 16 is sufficient for immortalization of human epithelial cells. J Virol. 1991 Jan;65(1):473–478. doi: 10.1128/jvi.65.1.473-478.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Harlow E., Franza B. R., Jr, Schley C. Monoclonal antibodies specific for adenovirus early region 1A proteins: extensive heterogeneity in early region 1A products. J Virol. 1985 Sep;55(3):533–546. doi: 10.1128/jvi.55.3.533-546.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Houweling A., van den Elsen P. J., van der Eb A. J. Partial transformation of primary rat cells by the leftmost 4.5% fragment of adenovirus 5 DNA. Virology. 1980 Sep;105(2):537–550. doi: 10.1016/0042-6822(80)90054-9. [DOI] [PubMed] [Google Scholar]
  33. Howes K. A., Ransom N., Papermaster D. S., Lasudry J. G., Albert D. M., Windle J. J. Apoptosis or retinoblastoma: alternative fates of photoreceptors expressing the HPV-16 E7 gene in the presence or absence of p53. Genes Dev. 1994 Jun 1;8(11):1300–1310. doi: 10.1101/gad.8.11.1300. [DOI] [PubMed] [Google Scholar]
  34. Kalvakolanu D. V., Bandyopadhyay S. K., Harter M. L., Sen G. C. Inhibition of interferon-inducible gene expression by adenovirus E1A proteins: block in transcriptional complex formation. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7459–7463. doi: 10.1073/pnas.88.17.7459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Kitajewski J., Schneider R. J., Safer B., Shenk T. An adenovirus mutant unable to express VAI RNA displays different growth responses and sensitivity to interferon in various host cell lines. Mol Cell Biol. 1986 Dec;6(12):4493–4498. doi: 10.1128/mcb.6.12.4493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Koutsky L. A., Galloway D. A., Holmes K. K. Epidemiology of genital human papillomavirus infection. Epidemiol Rev. 1988;10:122–163. doi: 10.1093/oxfordjournals.epirev.a036020. [DOI] [PubMed] [Google Scholar]
  37. Lewis A. M., Jr, Cook J. L. A new role for DNA virus early proteins in viral carcinogenesis. Science. 1985 Jan 4;227(4682):15–20. doi: 10.1126/science.3843807. [DOI] [PubMed] [Google Scholar]
  38. Lewis A. M., Jr, Cook J. L. The interface between adenovirus-transformed cells and cellular immune response in the challenged host. Curr Top Microbiol Immunol. 1984;110:1–22. doi: 10.1007/978-3-642-46494-2_1. [DOI] [PubMed] [Google Scholar]
  39. Malejczyk J., Majewski S., Jablonska S., Rogozinski T. T., Orth G. Abrogated NK-cell lysis of human papillomavirus (HPV)-16-bearing keratinocytes in patients with pre-cancerous and cancerous HPV-induced anogenital lesions. Int J Cancer. 1989 Feb 15;43(2):209–214. doi: 10.1002/ijc.2910430206. [DOI] [PubMed] [Google Scholar]
  40. Malejczyk J., Malejczyk M., Urbanski A., Köck A., Jablonska S., Orth G., Luger T. A. Constitutive release of IL6 by human papillomavirus type 16 (HPV16)-harboring keratinocytes: a mechanism augmenting the NK-cell-mediated lysis of HPV-bearing neoplastic cells. Cell Immunol. 1991 Aug;136(1):155–164. doi: 10.1016/0008-8749(91)90390-w. [DOI] [PubMed] [Google Scholar]
  41. Mymryk J. S., Shire K., Bayley S. T. Induction of apoptosis by adenovirus type 5 E1A in rat cells requires a proliferation block. Oncogene. 1994 Apr;9(4):1187–1193. [PubMed] [Google Scholar]
  42. Münger K., Phelps W. C., Bubb V., Howley P. M., Schlegel R. The E6 and E7 genes of the human papillomavirus type 16 together are necessary and sufficient for transformation of primary human keratinocytes. J Virol. 1989 Oct;63(10):4417–4421. doi: 10.1128/jvi.63.10.4417-4421.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Nawa A., Nishiyama Y., Yamamoto N., Maeno K., Goto S., Tomoda Y. Selective suppression of human papilloma virus type 18 mRNA level in HeLa cells by interferon. Biochem Biophys Res Commun. 1990 Jul 31;170(2):793–799. doi: 10.1016/0006-291x(90)92161-r. [DOI] [PubMed] [Google Scholar]
  44. Nielsch U., Pine R., Zimmer S. G., Babiss L. E. Induced expression of the endogenous beta interferon gene in adenovirus type 5-transformed rat fibroblasts. J Virol. 1992 Apr;66(4):1884–1890. doi: 10.1128/jvi.66.4.1884-1890.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Pan H., Griep A. E. Altered cell cycle regulation in the lens of HPV-16 E6 or E7 transgenic mice: implications for tumor suppressor gene function in development. Genes Dev. 1994 Jun 1;8(11):1285–1299. doi: 10.1101/gad.8.11.1285. [DOI] [PubMed] [Google Scholar]
  46. Phelps W. C., Yee C. L., Münger K., Howley P. M. The human papillomavirus type 16 E7 gene encodes transactivation and transformation functions similar to those of adenovirus E1A. Cell. 1988 May 20;53(4):539–547. doi: 10.1016/0092-8674(88)90570-3. [DOI] [PubMed] [Google Scholar]
  47. Pietenpol J. A., Stein R. W., Moran E., Yaciuk P., Schlegel R., Lyons R. M., Pittelkow M. R., Münger K., Howley P. M., Moses H. L. TGF-beta 1 inhibition of c-myc transcription and growth in keratinocytes is abrogated by viral transforming proteins with pRB binding domains. Cell. 1990 Jun 1;61(5):777–785. doi: 10.1016/0092-8674(90)90188-k. [DOI] [PubMed] [Google Scholar]
  48. Pitkäranta A., Hovi T. Induction of interferon in human leukocyte cultures by natural pathogenic respiratory viruses. J Interferon Res. 1993 Dec;13(6):423–426. doi: 10.1089/jir.1993.13.423. [DOI] [PubMed] [Google Scholar]
  49. Rao L., Debbas M., Sabbatini P., Hockenbery D., Korsmeyer S., White E. The adenovirus E1A proteins induce apoptosis, which is inhibited by the E1B 19-kDa and Bcl-2 proteins. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7742–7746. doi: 10.1073/pnas.89.16.7742. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Routes J. M. Adenovirus E1A inhibits IFN-induced resistance to cytolysis by natural killer cells. J Immunol. 1993 May 15;150(10):4315–4322. [PubMed] [Google Scholar]
  51. Routes J. M., Cook J. L. Adenovirus persistence in man. Defective E1A gene product targeting of infected cells for elimination by natural killer cells. J Immunol. 1989 Jun 1;142(11):4022–4026. [PubMed] [Google Scholar]
  52. Routes J. M., Cook J. L. E1A gene expression induces susceptibility to killing by NK cells following immortalization but not adenovirus infection of human cells. Virology. 1995 Jul 10;210(2):421–428. doi: 10.1006/viro.1995.1358. [DOI] [PubMed] [Google Scholar]
  53. Routes J. M. IFN increases class I MHC antigen expression on adenovirus-infected human cells without inducing resistance to natural killer cell killing. J Immunol. 1992 Oct 1;149(7):2372–2377. [PubMed] [Google Scholar]
  54. Routes J. M., Metz B. A., Cook J. L. Endogenous expression of E1A in human cells enhances the effect of adenovirus E3 on class I major histocompatibility complex antigen expression. J Virol. 1993 Jun;67(6):3176–3181. doi: 10.1128/jvi.67.6.3176-3181.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Sawada Y., Föhring B., Shenk T. E., Raska K., Jr Tumorigenicity of adenovirus-transformed cells: region E1A of adenovirus 12 confers resistance to natural killer cells. Virology. 1985 Dec;147(2):413–421. doi: 10.1016/0042-6822(85)90143-6. [DOI] [PubMed] [Google Scholar]
  56. 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]
  57. Schwarz E., Freese U. K., Gissmann L., Mayer W., Roggenbuck B., Stremlau A., zur Hausen H. Structure and transcription of human papillomavirus sequences in cervical carcinoma cells. Nature. 1985 Mar 7;314(6006):111–114. doi: 10.1038/314111a0. [DOI] [PubMed] [Google Scholar]
  58. Sheil J. M., Gallimore P. H., Zimmer S. G., Sopori M. L. Susceptibility of Adenovirus 2-transformed rat cell lines to natural killer (NK) cells: direct correlation between NK resistance and in vivo tumorigenesis. J Immunol. 1984 Mar;132(3):1578–1582. [PubMed] [Google Scholar]
  59. Sims S. H., Cha Y., Romine M. F., Gao P. Q., Gottlieb K., Deisseroth A. B. A novel interferon-inducible domain: structural and functional analysis of the human interferon regulatory factor 1 gene promoter. Mol Cell Biol. 1993 Jan;13(1):690–702. doi: 10.1128/mcb.13.1.690. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Smotkin D., Wettstein F. O. Transcription of human papillomavirus type 16 early genes in a cervical cancer and a cancer-derived cell line and identification of the E7 protein. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4680–4684. doi: 10.1073/pnas.83.13.4680. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Sosa M. A., DeGasperi R., Fazely F., Ruprecht R. M. Human cell lines stably expressing HIV env and tat gene products. Biochem Biophys Res Commun. 1989 May 30;161(1):305–311. doi: 10.1016/0006-291x(89)91597-0. [DOI] [PubMed] [Google Scholar]
  62. Tay S. K., Jenkins D., Singer A. Natural killer cells in cervical intraepithelial neoplasia and human papillomavirus infection. Br J Obstet Gynaecol. 1987 Sep;94(9):901–906. doi: 10.1111/j.1471-0528.1987.tb03763.x. [DOI] [PubMed] [Google Scholar]
  63. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Trinchieri G., Matsumoto-Kobayashi M., Clark S. C., Seehra J., London L., Perussia B. Response of resting human peripheral blood natural killer cells to interleukin 2. J Exp Med. 1984 Oct 1;160(4):1147–1169. doi: 10.1084/jem.160.4.1147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Trinchieri G., Santoli D., Knowles B. B. Tumour cell lines induce interferon in human lymphocytes. Nature. 1977 Dec 15;270(5638):611–613. doi: 10.1038/270611a0. [DOI] [PubMed] [Google Scholar]
  66. Vousden K. H., Jat P. S. Functional similarity between HPV16E7, SV40 large T and adenovirus E1a proteins. Oncogene. 1989 Feb;4(2):153–158. [PubMed] [Google Scholar]
  67. Vousden K. Interactions of human papillomavirus transforming proteins with the products of tumor suppressor genes. FASEB J. 1993 Jul;7(10):872–879. doi: 10.1096/fasebj.7.10.8393818. [DOI] [PubMed] [Google Scholar]
  68. Walker T. A., Wilson B. A., Lewis A. M., Jr, Cook J. L. E1A oncogene induction of cytolytic susceptibility eliminates sarcoma cell tumorigenicity. Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6491–6495. doi: 10.1073/pnas.88.15.6491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Woodworth C. D., Lichti U., Simpson S., Evans C. H., DiPaolo J. A. Leukoregulin and gamma-interferon inhibit human papillomavirus type 16 gene transcription in human papillomavirus-immortalized human cervical cells. Cancer Res. 1992 Jan 15;52(2):456–463. [PubMed] [Google Scholar]
  70. Yee C., Krishnan-Hewlett I., Baker C. C., Schlegel R., Howley P. M. Presence and expression of human papillomavirus sequences in human cervical carcinoma cell lines. Am J Pathol. 1985 Jun;119(3):361–366. [PMC free article] [PubMed] [Google Scholar]
  71. 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]
  72. Zantema A., Schrier P. I., Davis-Olivier A., van Laar T., Vaessen R. T., van der EB A. J. Adenovirus serotype determines association and localization of the large E1B tumor antigen with cellular tumor antigen p53 in transformed cells. Mol Cell Biol. 1985 Nov;5(11):3084–3091. doi: 10.1128/mcb.5.11.3084. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. zur Hausen H. Viruses in human cancers. Science. 1991 Nov 22;254(5035):1167–1173. doi: 10.1126/science.1659743. [DOI] [PubMed] [Google Scholar]

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