DNA:EBMA-1 Interactions and Latency of Epstein-Barr Virus

Abstract

During latent infection EBV genomes are maintained as nucleosome-covered episomes. Recombinant DNA vectors carrying the EBV plasmid origin of replication (ori-P) are maintained in transfected cells in an unintegrated state if EBNA-1 is being concomitantly expressed in the cells (1). Thus EBNA-1 is the only viral protein required, in addition to the cellular replication machinery, to replicate the episomal form of the EBV genome. The EBV origin of plasmid replication is located within an 1800bp segment (bases 7,334 to 9,519 of the EBV genome) and consists of two essential domains, Region I (family of repeats) and Region II (the dyad symmetry) that are separated by approximately 1000bp. (2,3). EBNA-1 mediates its replication function through sequence-specific binding to the two domains of ori-P. Rawlins et al. (4) showed by DNAase I protection studies that Region I of ori-P consists of 20 tandemly repeated binding sites for EBNA-1 while Region II contains 4 overlapping binding sites. An additional binding locus (Region III) was also identified in a separate region of the genome in BamHI-Q.