Characterization of the minimal replicator of Kaposi's sarcoma-associated herpesvirus latent origin

The latency-associated nuclear antigen (LANA) of Kaposi's sarcoma-associated herpesvirus (KSHV) binds to two sites within the 801-bp-long terminal repeat (TR) and is the only viral protein required for episomal maintenance. While two or more copies of TR are required for long-term maintenance, a single TR confers LANA-dependent origin activity on plasmid DNA. Deletion mapping revealed a 71-bp-long minimal replicator containing two distinctive sequence elements: LANA binding sites (LBS1/2) and an adjacent 29- to 32-bp-long GC-rich sequence which we termed the replication element. Furthermore, the transcription factor Sp1 can bind to TR outside the minimal replicator and contributes to TR's previously reported enhancer activity.