Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1990 Sep;64(9):4329–4337. doi: 10.1128/jvi.64.9.4329-4337.1990

Defective expression of adenovirus genes during early infection of undifferentiated OTF963 embryonal carcinoma cells.

C C Nelson 1, A W Braithwaite 1, M Silvestro 1, A J Bellett 1
PMCID: PMC247900  PMID: 2143541

Abstract

Adenovirus infection was compared in F9 (OTF963) cells and cells induced to differentiate with retinoic acid, in order to study expression of early genes under the control of the reported "E1a-like factor" in F9 cells. However, not only was transcription of the viral E1a gene defective in undifferentiated cells but expression of all the other early genes was found to be reduced in OTF963 cells in comparison to differentiated cells. The defect in early gene expression was detected at the level of transcriptional initiation during the first 48 h of infection and resulted in similarly low levels of viral cytoplasmic mRNA and viral protein synthesis. Viral DNA replication was delayed and reduced. After 48 h of infection, the defect in transcription in OTF963 cells of E1a and other early genes was relieved, so that by 72 h postinfection the level of transcription was similar to that 16 h after infection of differentiated cells. At no time did adenovirus early gene expression occur independently of viral E1a. These results suggest limits to the generality and explanatory power of the hypothesis that F9 embryonal carcinoma cells contain an E1a-like factor.

Full text

PDF
4329

Images in this article

4331Image
on p.4331
4332Image
on p.4332
4333Image
on p.4333
4333Image
on p.4333
4334Image
on p.4334

Selected References

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

  1. Babiss L. E. The cellular transcription factor E2f requires viral E1A and E4 gene products for increased DNA-binding activity and functions to stimulate adenovirus E2A gene expression. J Virol. 1989 Jun;63(6):2709–2717. doi: 10.1128/jvi.63.6.2709-2717.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bagchi S., Raychaudhuri P., Nevins J. R. Phosphorylation-dependent activation of the adenovirus-inducible E2F transcription factor in a cell-free system. Proc Natl Acad Sci U S A. 1989 Jun;86(12):4352–4356. doi: 10.1073/pnas.86.12.4352. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bellett A. J., Li P., David E. T., Mackey E. J., Braithwaite A. W., Cutt J. R. Control functions of adenovirus transformation region E1A gene products in rat and human cells. Mol Cell Biol. 1985 Aug;5(8):1933–1939. doi: 10.1128/mcb.5.8.1933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Berk A. J., Lee F., Harrison T., Williams J., Sharp P. A. Pre-early adenovirus 5 gene product regulates synthesis of early viral messenger RNAs. Cell. 1979 Aug;17(4):935–944. doi: 10.1016/0092-8674(79)90333-7. [DOI] [PubMed] [Google Scholar]
  5. Borrelli E., Hen R., Chambon P. Adenovirus-2 E1A products repress enhancer-induced stimulation of transcription. Nature. 1984 Dec 13;312(5995):608–612. doi: 10.1038/312608a0. [DOI] [PubMed] [Google Scholar]
  6. Braithwaite A. W., Jenkins J. R. Ability of p53 and the adenovirus E1b 58-kilodalton protein to form a complex is determined by p53. J Virol. 1989 Apr;63(4):1792–1799. doi: 10.1128/jvi.63.4.1792-1799.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cheng C., Praszkier J. Regulation of type 5 adenovirus replication in murine teratocarcinoma cell lines. Virology. 1982 Nov;123(1):45–59. doi: 10.1016/0042-6822(82)90293-8. [DOI] [PubMed] [Google Scholar]
  8. Dean M., Levine R. A., Campisi J. c-myc regulation during retinoic acid-induced differentiation of F9 cells is posttranscriptional and associated with growth arrest. Mol Cell Biol. 1986 Feb;6(2):518–524. doi: 10.1128/mcb.6.2.518. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Feuer G., Taketo M., Hanecak R. C., Fan H. Two blocks in Moloney murine leukemia virus expression in undifferentiated F9 embryonal carcinoma cells as determined by transient expression assays. J Virol. 1989 May;63(5):2317–2324. doi: 10.1128/jvi.63.5.2317-2324.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fujimura F. K., Deininger P. L., Friedmann T., Linney E. Mutation near the polyoma DNA replication origin permits productive infection of F9 embryonal carcinoma cells. Cell. 1981 Mar;23(3):809–814. doi: 10.1016/0092-8674(81)90445-1. [DOI] [PubMed] [Google Scholar]
  12. Gautsch J. W., Wilson M. C. Delayed de novo methylation in teratocarcinoma suggests additional tissue-specific mechanisms for controlling gene expression. Nature. 1983 Jan 6;301(5895):32–37. doi: 10.1038/301032a0. [DOI] [PubMed] [Google Scholar]
  13. Gorman C. M., Rigby P. W., Lane D. P. Negative regulation of viral enhancers in undifferentiated embryonic stem cells. Cell. 1985 Sep;42(2):519–526. doi: 10.1016/0092-8674(85)90109-6. [DOI] [PubMed] [Google Scholar]
  14. Grover A., Adamson E. D. Evidence for the existence of an early common biochemical pathway in the differentiation of F9 cells into visceral or parietal endoderm: modulation by cyclic AMP. Dev Biol. 1986 Apr;114(2):492–503. doi: 10.1016/0012-1606(86)90213-7. [DOI] [PubMed] [Google Scholar]
  15. Hearing P., Shenk T. The adenovirus type 5 E1A enhancer contains two functionally distinct domains: one is specific for E1A and the other modulates all early units in cis. Cell. 1986 Apr 25;45(2):229–236. doi: 10.1016/0092-8674(86)90387-9. [DOI] [PubMed] [Google Scholar]
  16. Hiebert S. W., Lipp M., Nevins J. R. E1A-dependent trans-activation of the human MYC promoter is mediated by the E2F factor. Proc Natl Acad Sci U S A. 1989 May;86(10):3594–3598. doi: 10.1073/pnas.86.10.3594. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Imperiale M. J., Kao H. T., Feldman L. T., Nevins J. R., Strickland S. Common control of the heat shock gene and early adenovirus genes: evidence for a cellular E1A-like activity. Mol Cell Biol. 1984 May;4(5):867–874. doi: 10.1128/mcb.4.5.867. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Jones N. C., Rigby P. W., Ziff E. B. Trans-acting protein factors and the regulation of eukaryotic transcription: lessons from studies on DNA tumor viruses. Genes Dev. 1988 Mar;2(3):267–281. doi: 10.1101/gad.2.3.267. [DOI] [PubMed] [Google Scholar]
  19. Jones N., Shenk T. An adenovirus type 5 early gene function regulates expression of other early viral genes. Proc Natl Acad Sci U S A. 1979 Aug;76(8):3665–3669. doi: 10.1073/pnas.76.8.3665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kao H. T., Nevins J. R. Transcriptional activation and subsequent control of the human heat shock gene during adenovirus infection. Mol Cell Biol. 1983 Nov;3(11):2058–2065. doi: 10.1128/mcb.3.11.2058. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kellermann O., Buc-Caron M. H., Gaillard J. Immortalization of precursors of endodermal, neuroectodermal and mesodermal lineages, following the introduction of the simian virus (SV40) early region into F9 cells. Differentiation. 1987;35(3):197–205. doi: 10.1111/j.1432-0436.1987.tb00169.x. [DOI] [PubMed] [Google Scholar]
  22. Kellermann O., Kelly F. Immortalization of early embryonic cell derivatives after the transfer of the early region of simian virus 40 into F9 teratocarcinoma cells. Differentiation. 1986;32(1):74–81. doi: 10.1111/j.1432-0436.1986.tb00558.x. [DOI] [PubMed] [Google Scholar]
  23. La Thangue N. B., Rigby P. W. The regulation of SV40 early gene expression in embryonal carcinoma stem cells--faithful transcriptional regulation in vitro. Nucleic Acids Res. 1988 Dec 23;16(24):11417–11430. doi: 10.1093/nar/16.24.11417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Linder S., Krondahl U., Sennerstam R., Ringertz N. R. Retinoic acid-induced differentiation of F9 embryonal carcinoma cells. Exp Cell Res. 1981 Apr;132(2):453–460. doi: 10.1016/0014-4827(81)90120-8. [DOI] [PubMed] [Google Scholar]
  25. Linial M., Gunderson N., Groudine M. Enhanced transcription of c-myc in bursal lymphoma cells requires continuous protein synthesis. Science. 1985 Dec 6;230(4730):1126–1132. doi: 10.1126/science.2999973. [DOI] [PubMed] [Google Scholar]
  26. Linney E., Davis B., Overhauser J., Chao E., Fan H. Non-function of a Moloney murine leukaemia virus regulatory sequence in F9 embryonal carcinoma cells. 1984 Mar 29-Apr 4Nature. 308(5958):470–472. doi: 10.1038/308470a0. [DOI] [PubMed] [Google Scholar]
  27. Lockett T. J., Sleigh M. J. Oncogene expression in differentiating F9 mouse embryonal carcinoma cells. Exp Cell Res. 1987 Dec;173(2):370–378. doi: 10.1016/0014-4827(87)90277-1. [DOI] [PubMed] [Google Scholar]
  28. Montano X., Lane D. P. The adenovirus Ela gene induces differentiation of F9 teratocarcinoma cells. Mol Cell Biol. 1987 May;7(5):1782–1790. doi: 10.1128/mcb.7.5.1782. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Nevins J. R. Mechanism of activation of early viral transcription by the adenovirus E1A gene product. Cell. 1981 Oct;26(2 Pt 2):213–220. doi: 10.1016/0092-8674(81)90304-4. [DOI] [PubMed] [Google Scholar]
  30. Niwa O., Yokota Y., Ishida H., Sugahara T. Independent mechanisms involved in suppression of the Moloney leukemia virus genome during differentiation of murine teratocarcinoma cells. Cell. 1983 Apr;32(4):1105–1113. doi: 10.1016/0092-8674(83)90294-5. [DOI] [PubMed] [Google Scholar]
  31. Onclercq R., Gilardi P., Lavenu A., Cremisi C. c-myc products trans-activate the adenovirus E4 promoter in EC stem cells by using the same target sequence as E1A products. J Virol. 1988 Dec;62(12):4533–4537. doi: 10.1128/jvi.62.12.4533-4537.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Paeratakul U., De Stasio P. R., Taylor M. W. A fast and sensitive method for detecting specific viral RNA in mammalian cells. J Virol. 1988 Apr;62(4):1132–1135. doi: 10.1128/jvi.62.4.1132-1135.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Reichel R., Kovesdi I., Nevins J. R. Developmental control of a promoter-specific factor that is also regulated by the E1A gene product. Cell. 1987 Feb 13;48(3):501–506. doi: 10.1016/0092-8674(87)90200-5. [DOI] [PubMed] [Google Scholar]
  34. Reichel R., Neill S. D., Kovesdi I., Simon M. C., Raychaudhuri P., Nevins J. R. The adenovirus E4 gene, in addition to the E1A gene, is important for trans-activation of E2 transcription and for E2F activation. J Virol. 1989 Sep;63(9):3643–3650. doi: 10.1128/jvi.63.9.3643-3650.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Rosenstraus M. J., Levine A. J. Alterations in the developmental potential of embryonal carcinoma cells in mixed aggregates of nullipotent and pluripotent cells. Cell. 1979 Jun;17(2):337–346. doi: 10.1016/0092-8674(79)90160-0. [DOI] [PubMed] [Google Scholar]
  36. Rosenstraus M. J., Sundell C. L., Liskay R. M. Cell-cycle characteristics of undifferentiated and differentiating embryonal carcinoma cells. Dev Biol. 1982 Feb;89(2):516–520. doi: 10.1016/0012-1606(82)90340-2. [DOI] [PubMed] [Google Scholar]
  37. Ross S. R., Levine A. J., Galos R. S., Williams J., Shenk T. Early viral proteins in HeLa cells infected with adenovirus type 5 host range mutants. Virology. 1980 Jun;103(2):475–492. doi: 10.1016/0042-6822(80)90205-6. [DOI] [PubMed] [Google Scholar]
  38. Sejersen T., Sümegi J., Ringertz N. R. Expression of cellular oncogenes in teratoma-derived cell lines. Exp Cell Res. 1985 Sep;160(1):19–30. doi: 10.1016/0014-4827(85)90232-0. [DOI] [PubMed] [Google Scholar]
  39. Sleigh M. J. Differential regulation of viral and cellular genes in F9 mouse embryonal carcinoma cells. Nucleic Acids Res. 1987 Nov 25;15(22):9379–9395. doi: 10.1093/nar/15.22.9379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Sleigh M. J., Lockett T. J., Kelly J., Lewy D. Competition studies with repressors and activators of viral enhancer function in F9 mouse embryonal carcinoma cells. Nucleic Acids Res. 1987 May 26;15(10):4307–4324. doi: 10.1093/nar/15.10.4307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Sleigh M. J., Lockett T. J. SV40 enhancer activation during retinoic acid-induced differentiation of F9 embryonal carcinoma cells. EMBO J. 1985 Dec 30;4(13B):3831–3837. doi: 10.1002/j.1460-2075.1985.tb04155.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Strickland S., Mahdavi V. The induction of differentiation in teratocarcinoma stem cells by retinoic acid. Cell. 1978 Oct;15(2):393–403. doi: 10.1016/0092-8674(78)90008-9. [DOI] [PubMed] [Google Scholar]
  43. Strickland S., Sawey M. J. Studies on the effect of retinoids on the differentiation of teratocarcinoma stem cells in vitro and in vivo. Dev Biol. 1980 Jul;78(1):76–85. doi: 10.1016/0012-1606(80)90319-x. [DOI] [PubMed] [Google Scholar]
  44. Strickland S., Smith K. K., Marotti K. R. Hormonal induction of differentiation in teratocarcinoma stem cells: generation of parietal endoderm by retinoic acid and dibutyryl cAMP. Cell. 1980 Sep;21(2):347–355. doi: 10.1016/0092-8674(80)90471-7. [DOI] [PubMed] [Google Scholar]
  45. Swartzendruber D. E., Friedrich T. D., Lehman J. M. Resistance of teratocarcinoma stem cells to infection with simian virus 40: early events. J Cell Physiol. 1977 Oct;93(1):25–30. doi: 10.1002/jcp.1040930105. [DOI] [PubMed] [Google Scholar]
  46. Swartzendruber D. E., Lehman J. M. Neoplastic differentiation: interaction of simian virus 40 and polyoma virus with murine teratocarcinoma cells in vitro. J Cell Physiol. 1975 Apr;85(2 Pt 1):179–187. doi: 10.1002/jcp.1040850204. [DOI] [PubMed] [Google Scholar]
  47. Teich N. M., Weiss R. A., Martin G. R., Lowy D. R. Virus infection of murine teratocarcinoma stem cell lines. Cell. 1977 Dec;12(4):973–982. doi: 10.1016/0092-8674(77)90162-3. [DOI] [PubMed] [Google Scholar]
  48. Trevor K., Lehman J. M. The interaction of polyoma virus with F9 embryonal carcinoma cells and chemically induced differentiated progeny: fate of the viral DNA and expression of viral antigens. J Cell Physiol Suppl. 1982;2:69–83. doi: 10.1002/jcp.1041130512. [DOI] [PubMed] [Google Scholar]
  49. Velcich A., Ziff E. Adenovirus E1a proteins repress transcription from the SV40 early promoter. Cell. 1985 Mar;40(3):705–716. doi: 10.1016/0092-8674(85)90219-3. [DOI] [PubMed] [Google Scholar]
  50. 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]
  51. Yee A. S., Reichel R., Kovesdi I., Nevins J. R. Promoter interaction of the E1A-inducible factor E2F and its potential role in the formation of a multi-component complex. EMBO J. 1987 Jul;6(7):2061–2068. doi: 10.1002/j.1460-2075.1987.tb02471.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Young K. S., Weigel R., Hiebert S., Nevins J. R. Adenovirus E1A-mediated negative control of genes activated during F9 differentiation. Mol Cell Biol. 1989 Jul;9(7):3109–3113. doi: 10.1128/mcb.9.7.3109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Zajchowski D. A., Jalinot P., Kedinger C. EIa-mediated stimulation of the adenovirus EIII promoter involves an enhancer element within the nearby EIIa promoter. J Virol. 1988 May;62(5):1762–1767. doi: 10.1128/jvi.62.5.1762-1767.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES