Nature 313, 812 - 815 (28 February 1985); doi:10.1038/313812a0

Stable replication of plasmids derived from Epstein−Barr virus in various mammalian cells

John L. Yates, Noreen Warren & Bill Sugden

McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, Wisconsin 53706, USA

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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