Conserved vRNA end sequences of Thogoto-orthomyxovirus suggest a new panhandle structure.

Panhandles are dsRNA structures formed by conserved sequences at the 5' and 3' ends of the influenza virus genomic RNA. They consist of two stems separated by a flexible bulge and serve as promoter for the viral polymerase. In the outer stem, melting of base pairs is a prerequisite for initiation of transcription. We compared the terminal sequences of Thogoto virus (THOV), a tick-borne orthomyxovirus, with those of influenza virus. Despite their overall similarity, the first U downstream of the 5' end of the panhandle (position 3 in influenza virus) is found at position 8 in the THOV sequence. This shift from position 3 to position 8 results in a radical change of the predicted secondary structure. In the outer stem, intra-strand base pairings are clearly favoured above inter-strand hybridizations. As this secondary structure can explain the functioning of a mutant promoter of influenza virus with twice the activity of the wild-type, we propose a general validity of our "hook-like" panhandle structure.