Skip to main content
Journal of Virology logoLink to Journal of Virology
. 1992 Jul;66(7):4612–4616. doi: 10.1128/jvi.66.7.4612-4616.1992

Phenotypes of Epstein-Barr virus LMP1 deletion mutants indicate transmembrane and amino-terminal cytoplasmic domains necessary for effects in B-lymphoma cells.

D Liebowitz 1, J Mannick 1, K Takada 1, E Kieff 1
PMCID: PMC241278  PMID: 1318423

Abstract

The Epstein-Barr virus (EBV) latent infection membrane protein 1 (LMP1) has previously been shown to cause EBV-negative B-lymphoma cells to grow in large clumps and to alter expression of surface activation and adhesion molecules (D. Wang, D. Liebowitz, F. Wang, C. Gregory, A. Rickinson, R. Larson, T. Springer, and E. Kieff, J. Virol. 62:1473-4184, 1988; F. Wang, C. Gregory, C. Sample, M. Rowe, D. Liebowitz, R. Murray, A. Rickinson, and E. Kieff, J. Virol. 64:2309-2318, 1990). In order to identify functional elements in the amino-terminal cytoplasmic domain and the first four transmembrane domains which were previously shown to be essential for LMP1 activity, three smaller deletion mutants were constructed and tested for their activity in B-lymphoma cells. The results of the present study indicate that the amino-terminal cytoplasmic domain, the first transmembrane domain, and the third and fourth transmembrane domains each contribute to LMP1's effects on B lymphocytes.

Full text

PDF
4612

Images in this article

Selected References

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

  1. Aman P., Lewin N., Nordström M., Klein G. EBV-activation of human B-lymphocytes. Curr Top Microbiol Immunol. 1986;132:266–271. doi: 10.1007/978-3-642-71562-4_40. [DOI] [PubMed] [Google Scholar]
  2. Baichwal V. R., Sugden B. The multiple membrane-spanning segments of the BNLF-1 oncogene from Epstein-Barr virus are required for transformation. Oncogene. 1989 Jan;4(1):67–74. [PubMed] [Google Scholar]
  3. Baichwal V. R., Sugden B. Transformation of Balb 3T3 cells by the BNLF-1 gene of Epstein-Barr virus. Oncogene. 1988 May;2(5):461–467. [PubMed] [Google Scholar]
  4. Clark E. A., Ledbetter J. A. Activation of human B cells mediated through two distinct cell surface differentiation antigens, Bp35 and Bp50. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4494–4498. doi: 10.1073/pnas.83.12.4494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dawson C. W., Rickinson A. B., Young L. S. Epstein-Barr virus latent membrane protein inhibits human epithelial cell differentiation. Nature. 1990 Apr 19;344(6268):777–780. doi: 10.1038/344777a0. [DOI] [PubMed] [Google Scholar]
  6. Fennewald S., van Santen V., Kieff E. Nucleotide sequence of an mRNA transcribed in latent growth-transforming virus infection indicates that it may encode a membrane protein. J Virol. 1984 Aug;51(2):411–419. doi: 10.1128/jvi.51.2.411-419.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fåhraeus R., Rymo L., Rhim J. S., Klein G. Morphological transformation of human keratinocytes expressing the LMP gene of Epstein-Barr virus. Nature. 1990 May 31;345(6274):447–449. doi: 10.1038/345447a0. [DOI] [PubMed] [Google Scholar]
  8. Henle W., Diehl V., Kohn G., Zur Hausen H., Henle G. Herpes-type virus and chromosome marker in normal leukocytes after growth with irradiated Burkitt cells. Science. 1967 Sep 1;157(3792):1064–1065. doi: 10.1126/science.157.3792.1064. [DOI] [PubMed] [Google Scholar]
  9. Hennessy K., Fennewald S., Hummel M., Cole T., Kieff E. A membrane protein encoded by Epstein-Barr virus in latent growth-transforming infection. Proc Natl Acad Sci U S A. 1984 Nov;81(22):7207–7211. doi: 10.1073/pnas.81.22.7207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Liebowitz D., Kieff E. Epstein-Barr virus latent membrane protein: induction of B-cell activation antigens and membrane patch formation does not require vimentin. J Virol. 1989 Sep;63(9):4051–4054. doi: 10.1128/jvi.63.9.4051-4054.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Liebowitz D., Kopan R., Fuchs E., Sample J., Kieff E. An Epstein-Barr virus transforming protein associates with vimentin in lymphocytes. Mol Cell Biol. 1987 Jul;7(7):2299–2308. doi: 10.1128/mcb.7.7.2299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Liebowitz D., Wang D., Kieff E. Orientation and patching of the latent infection membrane protein encoded by Epstein-Barr virus. J Virol. 1986 Apr;58(1):233–237. doi: 10.1128/jvi.58.1.233-237.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Mann K. P., Staunton D., Thorley-Lawson D. A. Epstein-Barr virus-encoded protein found in plasma membranes of transformed cells. J Virol. 1985 Sep;55(3):710–720. doi: 10.1128/jvi.55.3.710-720.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Mann K. P., Thorley-Lawson D. Posttranslational processing of the Epstein-Barr virus-encoded p63/LMP protein. J Virol. 1987 Jul;61(7):2100–2108. doi: 10.1128/jvi.61.7.2100-2108.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Martin J., Sugden B. Transformation by the oncogenic latent membrane protein correlates with its rapid turnover, membrane localization, and cytoskeletal association. J Virol. 1991 Jun;65(6):3246–3258. doi: 10.1128/jvi.65.6.3246-3258.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Nilsson K., Klein G. Phenotypic and cytogenetic characteristics of human B-lymphoid cell lines and their relevance for the etiology of Burkitt's lymphoma. Adv Cancer Res. 1982;37:319–380. doi: 10.1016/s0065-230x(08)60886-6. [DOI] [PubMed] [Google Scholar]
  17. Patarroyo M., Beatty P. G., Nilsson K., Gahmberg C. G. Identification of a cell-surface glycoprotein mediating cell adhesion in EBV-immortalized normal B cells. Int J Cancer. 1986 Oct 15;38(4):539–547. doi: 10.1002/ijc.2910380414. [DOI] [PubMed] [Google Scholar]
  18. Pope J. H., Horne M. K., Scott W. Transformation of foetal human keukocytes in vitro by filtrates of a human leukaemic cell line containing herpes-like virus. Int J Cancer. 1968 Nov 15;3(6):857–866. doi: 10.1002/ijc.2910030619. [DOI] [PubMed] [Google Scholar]
  19. Rothlein R., Dustin M. L., Marlin S. D., Springer T. A. A human intercellular adhesion molecule (ICAM-1) distinct from LFA-1. J Immunol. 1986 Aug 15;137(4):1270–1274. [PubMed] [Google Scholar]
  20. Rowe M., Hildreth J. E., Rickinson A. B., Epstein M. A. Monoclonal antibodies to Epstein-Barr virus-induced, transformation-associated cell surface antigens: binding patterns and effect upon virus-specific T-cell cytotoxicity. Int J Cancer. 1982 Apr 15;29(4):373–381. doi: 10.1002/ijc.2910290403. [DOI] [PubMed] [Google Scholar]
  21. Thorley-Lawson D. A., Mann K. P. Early events in Epstein-Barr virus infection provide a model for B cell activation. J Exp Med. 1985 Jul 1;162(1):45–59. doi: 10.1084/jem.162.1.45. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Thorley-Lawson D. A., Nadler L. M., Bhan A. K., Schooley R. T. BLAST-2 [EBVCS], an early cell surface marker of human B cell activation, is superinduced by Epstein Barr virus. J Immunol. 1985 May;134(5):3007–3012. [PubMed] [Google Scholar]
  23. Wang D., Liebowitz D., Kieff E. An EBV membrane protein expressed in immortalized lymphocytes transforms established rodent cells. Cell. 1985 Dec;43(3 Pt 2):831–840. doi: 10.1016/0092-8674(85)90256-9. [DOI] [PubMed] [Google Scholar]
  24. Wang D., Liebowitz D., Kieff E. The truncated form of the Epstein-Barr virus latent-infection membrane protein expressed in virus replication does not transform rodent fibroblasts. J Virol. 1988 Jul;62(7):2337–2346. doi: 10.1128/jvi.62.7.2337-2346.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Wang D., Liebowitz D., Wang F., Gregory C., Rickinson A., Larson R., Springer T., Kieff E. Epstein-Barr virus latent infection membrane protein alters the human B-lymphocyte phenotype: deletion of the amino terminus abolishes activity. J Virol. 1988 Nov;62(11):4173–4184. doi: 10.1128/jvi.62.11.4173-4184.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Wang F., Gregory C., Sample C., Rowe M., Liebowitz D., Murray R., Rickinson A., Kieff E. Epstein-Barr virus latent membrane protein (LMP1) and nuclear proteins 2 and 3C are effectors of phenotypic changes in B lymphocytes: EBNA-2 and LMP1 cooperatively induce CD23. J Virol. 1990 May;64(5):2309–2318. doi: 10.1128/jvi.64.5.2309-2318.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Wilson J. B., Weinberg W., Johnson R., Yuspa S., Levine A. J. Expression of the BNLF-1 oncogene of Epstein-Barr virus in the skin of transgenic mice induces hyperplasia and aberrant expression of keratin 6. Cell. 1990 Jun 29;61(7):1315–1327. doi: 10.1016/0092-8674(90)90695-b. [DOI] [PubMed] [Google Scholar]

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

RESOURCES