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 latently infected. We have isolated, sequenced, and functionally characterized the EBNA1 gene of herpesvirus papio (HVP), an EBV-like virus that infects baboons. The amino acid sequences of EBNA1 of HVP and EBV are 56% identical, if the difference in the length of the glycine and alanine containing repetitive region, which is much shorter for HVP EBNA1, 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 thought to be most critical for DNA binding. Most of the salient features of the amino-terminal two-thirds of EBNA1 (the amino-terminal domain), including a dearth of sequences predictive of alpha-helical or beta-sheet 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 resemble the amino terminus of rat ribosomal protein S2. Plasmids carrying oriP of either virus replicated stably in mammalian cells and supported efficient outgrowth of colonies under selection when supported by EBNA1 from either virus, although with each oriP there was a noticeable preference for EBNA1 to be from the same virus. HVP EBNA1 was less effective than EBV EBNA1 at activating the enhancer function of EBV oriP and under certain conditions was less effective than EBV EBNA1 at supporting 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 responsible for the differences in transcriptional activation and plasmid maintenance, respectively. The results showed that changes within EBNA1 can differentially alter its transcriptional and replicational activities. (C) 1996 Academic Press, Inc.