Abstract
A previously unrecognized activity has been associated with the product of the BNLF-1 gene of Epstein-Barr virus. This gene encodes the latent membrane protein of Epstein-Barr virus. When the gene was expressed at high levels, it was toxic to all cell lines tested, which included six human B-lymphoid lines as well as BALB/3T3, 143/EBNA-1, and HEp-2 cells. The BNLF-1 gene was previously shown to induce anchorage-independent and tumorigenic growth in Rat-1 and BALB/3T3 cells. We demonstrate here that only those mutations in the BNLF-1 gene that score positively in the anchorage-independent growth assay were cytotoxic when expressed at high levels. It is therefore possible that the same activities of the latent membrane protein that are necessary to induce anchorage-independent growth of some rodent cell lines also confer toxicity to many cell lines when expressed at high levels.
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- Baer R., Bankier A. T., Biggin M. D., Deininger P. L., Farrell P. J., Gibson T. J., Hatfull G., Hudson G. S., Satchwell S. C., Séguin C. DNA sequence and expression of the B95-8 Epstein-Barr virus genome. Nature. 1984 Jul 19;310(5974):207–211. doi: 10.1038/310207a0. [DOI] [PubMed] [Google Scholar]
- Baichwal V. R., Sugden B. Posttranslational processing of an Epstein-Barr virus-encoded membrane protein expressed in cells transformed by Epstein-Barr virus. J Virol. 1987 Mar;61(3):866–875. doi: 10.1128/jvi.61.3.866-875.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Bankier A. T., Deininger P. L., Satchwell S. C., Baer R., Farrell P. J., Barrell B. G. DNA sequence analysis of the EcoRI Dhet fragment of B95-8 Epstein-Barr virus containing the terminal repeat sequences. Mol Biol Med. 1983 Nov;1(4):425–445. [PubMed] [Google Scholar]
- 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]
- Foecking M. K., Hofstetter H. Powerful and versatile enhancer-promoter unit for mammalian expression vectors. Gene. 1986;45(1):101–105. doi: 10.1016/0378-1119(86)90137-x. [DOI] [PubMed] [Google Scholar]
- Goff S. P., Tabin C. J., Wang J. Y., Weinberg R., Baltimore D. Transfection of fibroblasts by cloned Abelson murine leukemia virus DNA and recovery of transmissible virus by recombination with helper virus. J Virol. 1982 Jan;41(1):271–285. doi: 10.1128/jvi.41.1.271-285.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Heston L., Rabson M., Brown N., Miller G. New Epstein-Barr virus variants from cellular subclones of P3J-HR-1 Burkitt lymphoma. Nature. 1982 Jan 14;295(5845):160–163. doi: 10.1038/295160a0. [DOI] [PubMed] [Google Scholar]
- Kavathas P., Bach F. H., DeMars R. Gamma ray-induced loss of expression of HLA and glyoxalase I alleles in lymphoblastoid cells. Proc Natl Acad Sci U S A. 1980 Jul;77(7):4251–4255. doi: 10.1073/pnas.77.7.4251. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Knutson J. C., Yee D. Electroporation: parameters affecting transfer of DNA into mammalian cells. Anal Biochem. 1987 Jul;164(1):44–52. doi: 10.1016/0003-2697(87)90365-4. [DOI] [PubMed] [Google Scholar]
- 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]
- PULVERTAFT J. V. A STUDY OF MALIGNANT TUMOURS IN NIGERIA BY SHORT-TERM TISSUE CULTURE. J Clin Pathol. 1965 May;18:261–273. doi: 10.1136/jcp.18.3.261. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pizzo P. A., Magrath I. T., Chattopadhyay S. K., Biggar R. J., Gerber P. A new tumour-derived transforming strain of Epstein-Barr virus. Nature. 1978 Apr 13;272(5654):629–631. doi: 10.1038/272629a0. [DOI] [PubMed] [Google Scholar]
- Reisman D., Sugden B. trans activation of an Epstein-Barr viral transcriptional enhancer by the Epstein-Barr viral nuclear antigen 1. Mol Cell Biol. 1986 Nov;6(11):3838–3846. doi: 10.1128/mcb.6.11.3838. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ricketts M. H., Levinson A. D. High-level expression of c-H-ras1 fails to fully transform rat-1 cells. Mol Cell Biol. 1988 Apr;8(4):1460–1468. doi: 10.1128/mcb.8.4.1460. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rowe M., Rowe D. T., Gregory C. D., Young L. S., Farrell P. J., Rupani H., Rickinson A. B. Differences in B cell growth phenotype reflect novel patterns of Epstein-Barr virus latent gene expression in Burkitt's lymphoma cells. EMBO J. 1987 Sep;6(9):2743–2751. doi: 10.1002/j.1460-2075.1987.tb02568.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schwartz R. C., Witte O. N. A recombinant murine retrovirus expressing v-rel is cytopathic. Virology. 1988 Jul;165(1):182–190. doi: 10.1016/0042-6822(88)90671-x. [DOI] [PubMed] [Google Scholar]
- Stinski M. F., Roehr T. J. Activation of the major immediate early gene of human cytomegalovirus by cis-acting elements in the promoter-regulatory sequence and by virus-specific trans-acting components. J Virol. 1985 Aug;55(2):431–441. doi: 10.1128/jvi.55.2.431-441.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sugden B., Marsh K., Yates J. A vector that replicates as a plasmid and can be efficiently selected in B-lymphoblasts transformed by Epstein-Barr virus. Mol Cell Biol. 1985 Feb;5(2):410–413. doi: 10.1128/mcb.5.2.410. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tarpley W. G., Temin H. M. The location of v-src in a retrovirus vector determines whether the virus is toxic or transforming. Mol Cell Biol. 1984 Dec;4(12):2653–2660. doi: 10.1128/mcb.4.12.2653. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Watanabe S. M., Witte O. N. Site-directed deletions of Abelson murine leukemia virus define 3' sequences essential for transformation and lethality. J Virol. 1983 Mar;45(3):1028–1036. doi: 10.1128/jvi.45.3.1028-1036.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yates J. L., Warren N., Sugden B. Stable replication of plasmids derived from Epstein-Barr virus in various mammalian cells. 1985 Feb 28-Mar 6Nature. 313(6005):812–815. doi: 10.1038/313812a0. [DOI] [PubMed] [Google Scholar]
- Ziegler S. F., Whitlock C. A., Goff S. P., Gifford A., Witte O. N. Lethal effect of the Abelson murine leukemia virus transforming gene product. Cell. 1981 Dec;27(3 Pt 2):477–486. doi: 10.1016/0092-8674(81)90389-5. [DOI] [PubMed] [Google Scholar]