Forty-Five Years of Marburg Virus Research

Brauburger, Kristina; Hume, Adam J.; Mühlberger, Elke; Olejnik, Judith

There are generally two types of genomic replication promoters for NNS RNA viruses: a bipartite promoter found in members of the paramyxovirus subfamily Paramyxovirinae and one continuous more compact replication promoter for rhabdo-and pneumoviruses [69] . The bipartite promoter structure of the Paramyxovirinae subfamily is associated with the "rule of six", i.e., the total genome length must be a multiple of six [70] . Given that filoviruses do not obey the rule of six, it was surprising that mapping of the MARV genomic replication promoter revealed a bipartite structure. The 3' genome end, the leader, comprises 48 nts and contains the first promoter element of the bipartite genomic replication promoter. The second promoter element consists of a (UNNNNN) 3 motif with three conserved uridine residues separated from each other by five non-conserved nucleotides. The UN (5) hexamers are located within the 3' untranslated region of the first MARV gene, the NP gene, and are separated from the first promoter region by the 12 nts long transcription start signal. Substitutions in the NP transcription start signal do not affect replication activity but do interfere with transcription initiation [71] . The 5' extracistronic region, the trailer, spans the last 75 nts of the MARV genome and contains the complement of the antigenomic replication promoter (see below, 8.2. Transcription and Replication). The structure of the MARV antigenomic promoter has not yet been determined. However, due to the presence of UN (5) hexamers it is likely that it is of bipartite nature, similar to the genomic promoter. A common feature of the leader and trailer regions of all NNS RNA viruses is a high degree of complementarity of the 10-15 most terminal 3' and 5' nucleotides [72] . Although filoviruses share this feature, both the leader and the trailer also have the capability to form an internal secondary structure, which is not the case for the leaders and trailers of other NNS RNA viruses [71, [73] [74] [75] .