Replication enhancer elements within the open reading frame of tick-borne encephalitis virus and their evolution within the Flavivirus genus

Tuplin, A.; Evans, D. J.; Buckley, A.; Jones, I. M.; Gould, E. A.; Gritsun, T. S.

It has recently been demonstrated that a short but highly conserved RNA hairpin (sHP) localized in the 3 0 -UTR of DENV2 RNA regulates the transition from a circular (required for the initiation of RNA replication) to linear RNA form during the progress of viral RNA synthesis (57) . The SL6-like structure of MBFV is localized immediately downstream of the 5 0 -CYCL (i.e. within the capsid gene, Supplementary Figure S1A ) suggesting it could also contribute to genome circularization. It is possible that in accord with the 3 0 sHP (highly conserved throughout the genus Flavivirus), it contributes to the unpairing of the 5 0 -3 0 -CYCL panhandle, to promote RNA elongation on the linear template. In contrast, the 5 0 -CYCL of TBFV is mapped to the 5 0 -UTR (i.e. upstream of the capsid gene, Figure 1A ) and therefore other tentative functions of the TBFV SL6 are not excluded, such as enhancing virus translation, RNA replication or playing a role in regulation between these processes; the possibility of a kissing-loop enhancer of genome circularization was previously discussed (17, 18, 23, 27, 43, 44) .