Structural features of the Seneca Valley virus internal ribosome entry site element ; 2 a picornavirus with a pestivirus - like IRES 3 4

25 The RNA genome of Seneca Valley Virus (SVV), a recently identified picornavirus, 26 contains an internal ribosome entry site (IRES) element which has structural and 27 functional similarity to that from classical swine fever virus and hepatitis C virus, 28 members of the flaviviridae. The SVV IRES has an absolute requirement for the presence 29 of a short region of virus coding sequence to allow it to function either in cells or in 30 rabbit reticulocyte lysate. The IRES activity does not require the translation initiation 31 factor eIF4A or intact eIF4G. The predicted secondary structure indicates that the SVV 32 IRES is more closely related to the CSFV IRES, including the presence of a bipartite IIId 33 domain. Mutagenesis of the SVV IRES, coupled to functional assays, support the core 34 elements of the IRES structure model, but surprisingly, deletion of the conserved IIId2 35 domain had no effect on IRES activity, including 40S and eIF3 binding. This is the first 36 example of a picornavirus IRES that is most closely related to the CSFV IRES and 37 suggests the possibility of multiple, independent, recombination events between the 38 genomes of the Picornaviridae and Flaviviridae to give rise to similar IRES elements. 39 40 Abstract word count: 190 41 42 Text word count: 6019 (inc. figure legends) 43 44