COMPARISON OF THE EBNA1 PROTEINS OF EPSTEIN-BARR-VIRUS AND HERPESVIRUS PAPIO IN SEQUENCE AND FUNCTION

The EBNA1 protein of Epstein-Barr virus (EBV) supports replication and maintenance of the circularized viral chromosome in cells that are la tently infected. We have isolated, sequenced, and functionally charact erized the EBNA1 gene of herpesvirus papio (HVP), an EBV-like virus th at infects baboons. The amino acid sequences of EBNA1 of HVP and EBV a re 56% identical, if the difference in the length of the glycine and a lanine containing repetitive region, which is much shorter for HVP EBN A1, is omitted for the calculation. The key structural features of the DNA-binding/dimerization domain (the carboxyl-terminal domain) appear to have been conserved, as have amino acids in the two regions though t to be most critical for DNA binding. Most of the salient features of the amino-terminal two-thirds of EBNA1 (the amino-terminal domain), i ncluding a dearth of sequences predictive of alpha-helical or beta-she et structures, are shared by the two sequences, although numerous gaps in this region were needed for alignment of the sequences. The amino- terminal fifty amino acids of EBNA1 of both EBV and HVP weakly resembl e the amino terminus of rat ribosomal protein S2. Plasmids carrying or iP of either virus replicated stably in mammalian cells and supported efficient outgrowth of colonies under selection when supported by EBNA 1 from either virus, although with each oriP there was a noticeable pr eference for EBNA1 to be from the same virus. HVP EBNA1 was less effec tive than EBV EBNA1 at activating the enhancer function of EBV oriP an d under certain conditions was less effective than EBV EBNA1 at suppor ting maintenance of plasmids carrying EBV oriP. Results obtained with hybrid EBNA1 molecules indicated that differences in the aminoterminal and carboxyl-terminal domains, respectively, are primarily responsibl e for the differences in transcriptional activation and plasmid mainte nance, respectively. The results showed that changes within EBNA1 can differentially alter its transcriptional and replicational activities. (C) 1996 Academic Press, Inc.