Origin and evolution of flavivirus 5′UTRs and panhandles: Trans-terminal duplications?

Flavivirus replication is mediated by interactions between complementary ssRNA sequences of the 5′- and 3′-termini that form dsRNA cyclisation stems or panhandles, varying in length, sequence and specific location in the mosquito-borne, tick-borne, non-vectored and non-classified flaviviruses. In this manuscript we manually aligned the flavivirus 5′UTRs and adjacent capsid genes and revealed significantly more homology than has hitherto been identified. Analysis of the alignments revealed that the panhandles represent evolutionary remnants of a long cyclisation domain that probably emerged through duplication of one of the UTR termini.