An additional complexity in flavivirus replication is the presence of replication enhancer elements (REEs) in the 3 0 -UTR that, while not obligatory for replication of laboratory-maintained viruses, are likely essential for virus circulation and transmission in nature (16, 18) . Engineered deletions or modifications of the REEs enable the recovery of viable viruses that are attenuated as a result of reduced RNA synthesis (10, (19) (20) (21) (22) . The cumulative effect of several REEs enhances the assembly of the RdRp complex and is probably critical to the survival of flaviviruses in nature (23) . The REEs identified for MBFV have become an important target for the development of a live attenuated vaccine for dengue virus (24, 25) .