Abstract
Epstein–Barr virus (EBV) infects human B lymphocytes, transforming the infected cells into dividing blasts that can proliferate indefinitely (see ref. 1 for a review). The viral genome of 172 kilobase pairs (kbp) is a plasmid in most transformed cells2–4. We have identified a region of EBV DNA, termed oriP (nucleotides 7,333–9,109 of strain B95–8), which acts in cis to permit linked DNAs to replicate as plasmids in cells containing EBV DNA5. We have postulated the existence of a trans-acting gene allowing oriP function. Here we report that this gene lies in a 2.6-kbp region of the viral genome (nucleotides 107, 567–110, 176) which encodes the EBNA-1 antigen6–8. We show that circular DNAs containing oriP, the EBNA-1 gene and a selectable marker replicate autonomously in cells derived from at least four developmental lineages and from at least three species. We also find that the one-third of the EBNA-1 gene repetitive in sequence is not essential for the trans-acting function that EBNA-1 gives oriP.
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References
zur Hausen, H. in DNA Tumor Viruses (ed. Tooze, T.) 747–795 (Cold Spring Harbor Laboratory, New York, 1981).
Nonoyama, M. & Pagano, J. S. Nature new Biol. 238, 169–171 (1972).
Lindahl, T. et al. J. molec. Biol. 102, 511–530 (1976).
Sugden, B., Phelps, M. & Domoradzki, J. J. Virol. 31, 590–595 (1979).
Yates, J., Warren, N., Reisman, D. & Sugden, B. Proc. natn. Acad. Sci. U.S.A. 81, 3806–3810 (1984).
Summers, W.P. et al. Proc. natn. Acad. Sci. U.S.A. 79, 5688–5692 (1982).
Hennessy, K., Heller, M., van Santen, V. & Kieff, E. Science 220, 1396–1398 (1983).
Hennessy, K. & Kieff, E. Proc. natn. Acad. Sci. U.S.A. 80, 5665–5669 (1983).
Fischer, D. K. et al. Proc. natn. Acad. Sci. U.S.A. 81, 43–47 (1984).
Baer, R. et al. Nature 310, 207–211 (1984).
van Santen, V., Cheung, A. & Kieff, E. Proc. natn. Acad. Sci. U.S.A. 78, 1930–1934 (1981).
Heller, M., van Santen, V. & Kieff, E. J. Virol. 44, 311–320 (1982).
Gritz, L. & Davies, J. Gene 25, 179–188 (1983).
Sugden, B., Marsh, K. & Yates, J. Molec. cell. Biol. (in the press).
Buell, G.N., Reisman, D., Kintner, C., Crouse, G. & Sugden, B. J. Virol. 40, 977–982 (1981).
Sassone-Corsi, P., Corden, J., Kedinger, C. & Chambon, P. Nucleic Acids Res. 9, 3941–3958 (1981).
Lescure, B. & Arcangioli, B. EMBO J. 3, 1067–1073 (1984).
Mulligan, R.C. & Berg, P. Proc. natn. Acad. Sci. U.S.A. 78, 2072–2076 (1981).
Henderson, A., Ripley, S., Heller, M. & Kieff, E. Proc. natn. Acad. Sci. U.S.A. 80, 1987–1991 (1983).
Graham, F. L. & Van der Eb, A. J. Virology 52, 456–467 (1973).
Schaffner, W. Proc. natn. Acad. Sci. U.S.A. 77, 2163–2167 (1980).
Neumann, E., Schaefer-Ridder, M., Wang, Y. & Hofschneider, P. H. EMBO J. 1, 841–845 (1982).
Szybalski, W., Szybalska, E. H. & Ragni, G. Natn. Cancer Inst. Monogr. 7, 75–89 (1962).
Graham, F. L., Bacchetti, S., McKinnon, R., Cordell, B. & Goodman, H. in Introduction of Macromolecules into Viable Mammalian Cells Vol. 1 (ed. Baserga, R.) 96–108 (Liss, New York, 1979).
Graham, F. L., Smiley, J., Russell, W. C. & Nairn, R. J. gen. Virol. 36, 59–72 (1977).
Lozzio, C. B. & Lozzio, B. B. Blood 45, 321–334 (1975).
Southern, E. M. J. molec. Biol. 98, 503–517 (1975).
Hirt, B. J. molec. Biol. 26, 365–369 (1967).
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Yates, J., Warren, N. & Sugden, B. Stable replication of plasmids derived from Epstein–Barr virus in various mammalian cells. Nature 313, 812–815 (1985). https://doi.org/10.1038/313812a0
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DOI: https://doi.org/10.1038/313812a0
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