1887

Journal of General Virology header logo

Volume 91, Issue 7

Adenovirus type 5 early encoded proteins of the E1 and E4 regions induce oncogenic transformation of primary rabbit cells Free

Abstract

Analysis of the molecular mechanisms of viral-mediated oncogenesis has contributed enormously to the understanding of the basic principles of normal/malignant cell growth. Transformation by human adenoviruses is a multi-step process involving the modulation of numerous cellular pathways, leading to inhibition of apoptosis and growth arrest. However, the molecular mechanism of how the adenovirus oncogenes facilitate transformation of rodent cells, while concurrently failing to do so for human cells, remains elusive. In this report, we demonstrate for the first time that the transformation capabilities of adenovirus type 5 oncogenes are not restricted to rodent cells, but include cells of the related mammalian order Lagomorpha, inducing considerable morphological alterations, enhanced cell growth and tumour induction . Furthermore, the established cell lines may represent a suitable tool for further development to generate E4-mutated adenoviruses, which has so far been difficult as mutations within the E4 region often prove to be lethal without a helper-cell system.

  • Received:
  • Accepted:
  • Published Online:
© SGM
Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.020537-0
2010-07-01
2024-04-16
Loading full text...

Full text loading...

/deliver/fulltext/jgv/91/7/1828.html?itemId=/content/journal/jgv/10.1099/vir.0.020537-0&mimeType=html&fmt=ahah

References

  1. Baker, A., Rohleder, K. J., Hanakahi, L. A. & Ketner, G.(2007). Adenovirus E4 34k and E1b 55k oncoproteins target host DNA ligase IV for proteasomal degradation. J Virol 81, 7034–7040.[CrossRef] [Google Scholar]
  2. Blanchette, P., Cheng, C. Y., Yan, Q., Ketner, G., Ornelles, D. A., Dobner, T., Conaway, R. C., Conaway, J. W. & Branton, P. E.(2004). Both BC-box motifs of adenovirus protein E4orf6 are required to efficiently assemble an E3 ligase complex that degrades p53. Mol Cell Biol 24, 9619–9629.[CrossRef] [Google Scholar]
  3. Branton, P. E., Bayley, S. T. & Graham, F. L.(1985). Transformation by human adenoviruses. Biochim Biophys Acta 780, 67–94. [Google Scholar]
  4. Byrd, P., Brown, K. W. & Gallimore, P. H.(1982). Malignant transformation of human embryo retinoblasts by cloned adenovirus 12 DNA. Nature 298, 69–71.[CrossRef] [Google Scholar]
  5. Catalucci, D., Sporeno, E., Cirillo, A., Ciliberto, G., Nicosia, A. & Colloca, S.(2005). An adenovirus type 5 (Ad5) amplicon-based packaging cell line for production of high-capacity helper-independent ΔE1–E2-E3–E4 Ad5 vectors. J Virol 79, 6400–6409.[CrossRef] [Google Scholar]
  6. Dallaire, F., Blanchette, P., Groitl, P., Dobner, T. & Branton, P. E.(2009). Identification of integrin α3 as a new substrate of the adenovirus E4orf6/E1B 55-kilodalton E3 ubiquitin ligase complex. J Virol 83, 5329–5338.[CrossRef] [Google Scholar]
  7. Endter, C. & Dobner, T.(2004). Cell transformation by human adenoviruses. Curr Top Microbiol Immunol 273, 163–214. [Google Scholar]
  8. Endter, C., Kzhyshkowska, J., Stauber, R. & Dobner, T.(2001). SUMO-1 modification required for transformation by adenovirus type 5 early region 1B 55-kDa oncoprotein. Proc Natl Acad Sci U S A 98, 11312–11317.[CrossRef] [Google Scholar]
  9. Endter, C., Hartl, B., Spruss, T., Hauber, J. & Dobner, T.(2005). Blockage of CRM1-dependent nuclear export of the adenovirus type 5 early region 1B 55-kDa protein augments oncogenic transformation of primary rat cells. Oncogene 24, 55–64.[CrossRef] [Google Scholar]
  10. Fallaux, F. J., Kranenburg, O., Cramer, S. J., Houweling, A., Van Ormondt, H., Hoeben, R. C. & Van Der Eb, A. J.(1996). Characterization of 911: a new helper cell line for the titration and propagation of early region 1-deleted adenoviral vectors. Hum Gene Ther 7, 215–222.[CrossRef] [Google Scholar]
  11. Fallaux, F. J., Bout, A., van der Velde, I., van den Wollenberg, D. J., Hehir, K. M., Keegan, J., Auger, C., Cramer, S. J., van Ormondt, H. & other authors(1998). New helper cells and matched early region 1-deleted adenovirus vectors prevent generation of replication-competent adenoviruses. Hum Gene Ther 9, 1909–1917.[CrossRef] [Google Scholar]
  12. Gallimore, P. H. & Turnell, A. S.(2001). Adenovirus E1A: remodelling the host cell, a life or death experience. Oncogene 20, 7824–7835.[CrossRef] [Google Scholar]
  13. Gallimore, P. H., Grand, R. J. & Byrd, P. J.(1986). Transformation of human embryo retinoblasts with simian virus 40, adenovirus and ras oncogenes. Anticancer Res 6, 499–508. [Google Scholar]
  14. Graham, F. L.(1984). Transformation by and oncogenicity of human adenoviruses. In The Adenoviruses, pp. 339–398. Edited by H. S. Ginsberg. New York: Plenum Press.
  15. Graham, F. L. & van der Eb, A. J.(1973). A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology 52, 456–467.[CrossRef] [Google Scholar]
  16. Graham, F. L., Smiley, J., Russel, W. C. & Nairn, R.(1977). Characteristics of a human cell line transformed by DNA from human adenovirus type 5. J Gen Virol 36, 59–72.[CrossRef] [Google Scholar]
  17. Graham, F. L., Rowe, D. T., McKinnon, R., Bacchetti, S., Ruben, M. & Branton, P. E.(1984). Transformation by human adenoviruses. J Cell Physiol Suppl 3, 151–163. [Google Scholar]
  18. Harlow, E., Pim, D. C. & Crawford, L. V.(1981). Complex of simian virus 40 large-T antigen and host 53,000-molecular-weight protein in monkey cells. J Virol 37, 564–573. [Google Scholar]
  19. Harlow, E., Franza, B. R., Jr & Schley, C.(1985). Monoclonal antibodies specific for adenovirus early region 1A proteins: extensive heterogeneity in early region 1A products. J Virol 55, 533–546. [Google Scholar]
  20. Hart, L. S., Ornelles, D. O. & Koumenis, C.(2006). The adenoviral E4ORF6 protein induces atypical apoptosis in response to DNA damage. J Biol Chem 282, 6061–6067.[CrossRef] [Google Scholar]
  21. Härtl, B., Zeller, T., Blanchette, P., Kremmer, E. & Dobner, T.(2008). Adenovirus type 5 early region 1B 55-kDa oncoprotein can promote cell transformation by a mechanism independent from blocking p53-activated transcription. Oncogene 27, 3673–3684.[CrossRef] [Google Scholar]
  22. Kao, C. C., Yew, P. R. & Berk, A. J.(1990). Domains required for in vitro association between the cellular p53 and the adenovirus 2 E1B 55K proteins. Virology 179, 806–814.[CrossRef] [Google Scholar]
  23. Kindsmüller, K., Schreiner, S., Leinenkugel, F., Groitl, P., Kremmer, E. & Dobner, T.(2009). A 49-kilodalton isoform of the adenovirus type 5 early region 1B 55-kilodalton protein is sufficient to support virus replication. J Virol 83, 9045–9056.[CrossRef] [Google Scholar]
  24. Logan, J., Pilder, S. & Shenk, T.(1984). Functional analysis of adenovirus type 5 early region 1B. Cancer Cells 2, 527–532. [Google Scholar]
  25. Lowe, S. W. & Ruley, H. E.(1993). Stabilization of the p53 tumor suppressor is induced by adenovirus 5 E1A and accompanies apoptosis. Genes Dev 7, 535–545.[CrossRef] [Google Scholar]
  26. Marton, M. J., Baim, S. B., Ornelles, D. A. & Shenk, T.(1990). The adenovirus E4 17-kilodalton protein complexes with the cellular transcription factor E2F, altering its DNA-binding properties and stimulating E1A-independent accumulation of E2 mRNA. J Virol 64, 2345–2359. [Google Scholar]
  27. Murphy, W. J., Eizirik, E., Johnson, W. E., Zhang, Y. P., Ryder, O. A. & O’Brien, S. J.(2001). Molecular phylogenetics and the origins of placental mammals. Nature 409, 614–618.[CrossRef] [Google Scholar]
  28. Nevels, M., Rubenwolf, S., Spruss, T., Wolf, H. & Dobner, T.(1997). The adenovirus E4orf6 protein can promote E1A/E1B-induced focus formation by interfering with p53 tumor suppressor function. Proc Natl Acad Sci U S A 94, 1206–1211.[CrossRef] [Google Scholar]
  29. Nevels, M., Spruss, T., Wolf, H. & Dobner, T.(1999a). The adenovirus E4orf6 protein contributes to malignant transformation by antagonizing E1A-induced accumulation of the tumor suppressor protein p53. Oncogene 18, 9–17.[CrossRef] [Google Scholar]
  30. Nevels, M., Täuber, B., Kremmer, E., Spruss, T., Wolf, H. & Dobner, T.(1999b). Transforming potential of the adenovirus type 5 E4orf3 protein. J Virol 73, 1591–1600. [Google Scholar]
  31. Nevels, M., Täuber, B., Spruss, T., Wolf, H. & Dobner, T.(2001). “Hit-and-run” transformation by adenovirus oncogenes. J Virol 75, 3089–3094.[CrossRef] [Google Scholar]
  32. Nevins, J. R. & Vogt, P. K.(1996). Cell transformation by viruses. In Virology, 3rd edn, pp. 301–343. Edited by B. N. Fields, D. M. Knipe & P. M. Howley. New York: Lippincott-Raven.
  33. Querido, E., Marcellus, R. C., Lai, A., Charbonneau, R., Teodoro, J. G., Ketner, G. & Branton, P. E.(1997). Regulation of p53 levels by the E1B 55-kilodalton protein and E4orf6 in adenovirus-infected cells. J Virol 71, 3788–3798. [Google Scholar]
  34. Querido, E., Blanchette, P., Yan, Q., Kamura, T., Morrison, M., Boivin, D., Kaelin, W. G., Conaway, R. C., Conaway, J. W. & Branton, P. E.(2001a). Degradation of p53 by adenovirus E4orf6 and E1B55K proteins occurs via a novel mechanism involving a Cullin-containing complex. Genes Dev 15, 3104–3117.[CrossRef] [Google Scholar]
  35. Querido, E., Morisson, M. R., Chu-Pham-Dang, H., Thirlwell, S. W., Boivin, D. & Branton, P. E.(2001b). Identification of three functions of the adenovirus E4orf6 protein that mediate p53 degradation by the E4orf6–E1B55K complex. J Virol 75, 699–709.[CrossRef] [Google Scholar]
  36. Ricciardi, R. P.(1995). Transformation and tumorigenesis mediated by the adenovirus E1A and E1B oncogenes. In DNA Tumor Viruses: Oncogenic Mechanisms, pp. 195–210. Edited by G. Barbanti-Brodano. New York: Plenum Press.
  37. Rubenwolf, S., Schütt, H., Nevels, M., Wolf, H. & Dobner, T.(1997). Structural analysis of the adenovirus type 5 E1B 55-kilodalton-E4orf6 protein complex. J Virol 71, 1115–1123. [Google Scholar]
  38. Sarnow, P., Ho, Y. S., Williams, J. & Levine, A. J.(1982). Adenovirus E1b-58kd tumor antigen and SV40 large tumor antigen are physically associated with the same 54 kd cellular protein in transformed cells. Cell 28, 387–394.[CrossRef] [Google Scholar]
  39. Schiedner, G., Hertel, S. & Kochanek, S.(2000). Efficient transformation of primary human amniocytes by E1 functions of Ad5: generation of new cell lines for adenoviral vector production. Hum Gene Ther 11, 2105–2116.[CrossRef] [Google Scholar]
  40. Stracker, T. H., Carson, C. T. & Weitzman, M. D.(2002). Adenovirus oncoproteins inactivate the Mre11 Rad50 NBS1 DNA repair complex. Nature 418, 348–352.[CrossRef] [Google Scholar]
  41. Täuber, B. & Dobner, T.(2001a). Adenovirus early E4 genes in viral oncogenesis. Oncogene 20, 7847–7854.[CrossRef] [Google Scholar]
  42. Täuber, B. & Dobner, T.(2001b). Molecular regulation and biological function of adenovirus early genes: the E4 ORFs. Gene 278, 1–23.[CrossRef] [Google Scholar]
  43. Trentin, J. J., Yabe, Y. & Taylor, G.(1962). The quest for human cancer viruses: a new approach to an old problem reveals cancer induction in hamster by human adenoviruses. Science 137, 835–849.[CrossRef] [Google Scholar]
  44. van den Heuvel, S. J. L., The, S. I., Klein, B., Jochemsen, A. G., Zantema, A. & van der Eb, A. J.(1992). p53 shares an antigenic determinant with proteins of 92 and 150 kilodaltons that may be involved in senescence of human cells. J Virol 66, 591–595. [Google Scholar]
  45. Whittaker, J. L., Byrd, P. J., Grand, R. J. & Gallimore, P. H.(1984). Isolation and characterization of four adenovirus type 12-transformed human embryo kidney cell lines. Mol Cell Biol 4, 110–116. [Google Scholar]
  46. Yew, P. R. & Berk, A. J.(1992). Inhibition of p53 transactivation required for transformation by adenovirus early 1B protein. Nature 357, 82–85.[CrossRef] [Google Scholar]
  47. Yew, P. R., Liu, X. & Berk, A. J.(1994). Adenovirus E1B oncoprotein tethers a transcriptional repression domain to p53. Genes Dev 8, 190–202.[CrossRef] [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.020537-0
Loading
Adenovirus type 5 early encoded proteins of the E1 and E4 regions induce oncogenic transformation of primary rabbit cells
J. Gen. Virol. 91, 1828 (2010); https://doi.org/10.1099/vir.0.020537-0
/content/journal/jgv/10.1099/vir.0.020537-0
/content/journal/jgv/10.1099/vir.0.020537-0
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error