The complete genome sequence of Seneca Valley virus (SVV) has been determined (Knowles and Hallenbeck, 2005; Hales et al., 2008; DQ641257) and shown to be most closely related to the Cardiovirus genus in the P1^cap (Fig. 1), 2C, 3C^pro and 3D^pol (Fig. 2) genome regions. However, in other genome areas, the 5’ UTR (IRES), Leader, 2B and 3A, SVV is very different to all other picornaviruses (no detectable similarity on database searches). The SVV 2A is a short peptide with a predicted ribosome-skipping mechanism characterized by a NPG^P motif similar to that found the aphthoviruses, erboviruses and teschoviruses and at the carboxy-terminus of the larger 2A of cardioviruses. The larger 2A of cardioviruses, lacking in SVV, inhibits cap-dependent mRNA translation (Aminev et al., 2003a) and cellular mRNA transcription (but not rRNA transcription; Aminev et al., 2003b). The SVV IRES is predicted to be related to that of hepatitis C virus (57% nt identity), porcine teschoviruses, avian encephalomyelitis virus, duck hepatitis virus 1 and members of a newly proposed picornavirus genus (which includes simian virus 2, porcine enterovirus 8 and duck picornavirus TW90A) (Hellen and de Breyne, 2007); this is very different to the cardiovirus type II IRES, which is similar to that of aphthoviruses (Jang et al., 1988). The cardiovirus leader polypeptide binds zinc, is phosphorylated during infection and plays a role in the regulation of viral genome translation (Dvorak et al., 2001), while the Leader of the aphthoviruses and erboviruses is a papain-like cysteine proteinase (Hinton et al., 2002). The SVV leader polypeptide lacks the catalytic residues necessary for proteolytic activity and does not contain either a zinc-finger motif [C-x-H-x(6)-C-x(2)C] in the leader amino-terminal region or a tyrosine phosphorylation motif [K-x(2)-E-x(2)-Y] approximately 14 residues downstream, possibly indicating a function distinct from that of both aphthoviruses and cardioviruses. SVV was first isolated as a cell culture contaminant, but has since been found in pigs throughout the United States (Knowles et al., 2006; Hales et al., unpublished data). There is no association with disease in pigs. In summary, although SVV is related to the cardioviruses in some genome regions, it is radically different in three proteins and the IRES. The Picornaviridae Study Group feels that these differences are too large, following precedent, to permit SVV to be classified as a cardiovirus. It is necessary therefore to create a new genus.

Aminev, A.G., Amineva, S.P. and Palmenberg, A.C. (2003a). Encephalomyocarditis viral protein 2A localizes to nucleoli and inhibits cap-dependent mRNA translation. Virus Res. 95: 45-57.

Aminev, A.G., Amineva, S.P. and Palmenberg AC. (2003b). Encephalomyocarditis virus (EMCV) proteins 2A and 3BCD localize to nuclei and inhibit cellular mRNA transcription but not rRNA transcription. Virus Res. 95: 59-73.

Dvorak, C.M., Hall, D.J., Hill, M., Riddle, M., Pranter, A., Dillman, J., Deibel, M. and Palmenberg, A.C. (2001).  Leader protein of encephalomyocarditis virus binds zinc, is phosphorylated during viral infection, and affects the efficiency of genome translation. Virology 290: 261-271.

Hales, L.M., Knowles, N.J., Reddy, P.S., Xu, L., Hay, C. and Hallenbeck, P.L. (2008). Complete genome sequence analysis of Seneca Valley virus-001, a novel oncolytic picornavirus. Journal of General Virology, in press.

Hales, L.M., Knowles, N.J. Jones, B.H., Landgraf, J.G., Swenson, S.L., House, J.A., Skele, K.L., Burroughs, K.D. and Hallenbeck, P.L. Swine are susceptible to infection with Seneca Valley virus, a new species of picornavirus. Unpublished.

Hellen, C.U.T. and de Breyne, S. (2007). A distinct group of hepacivirus/pestivirus-like internal ribosomal entry sites in members of diverse picornavirus genera: evidence for modular exchange of functional noncoding RNA elements by recombination. J. Virol. 81: 5850-5863.

Hinton, T.M., Ross-Smith, N., Warner, S., Belsham, G.J. and Crabb, B.S. (2002). Conservation of L and 3C proteinase activities across distantly related aphthoviruses. J Gen Virol. 83: 3111-3121.

Jang, S.K., Krausslich, H.G., Nicklin, M.J., Duke, G.M., Palmenberg, A.C. and Wimmer, E. (1988). A segment of the 5' nontranslated region of encephalomyocarditis virus RNA directs internal entry of ribosomes during in vitro translation. J. Virol. 62: 2636–2643.

Knowles, N.J. and Hallenbeck, P.L. (2005). A new picornavirus is most closely related to cardioviruses. EUROPIC 2005: XIII^th Meeting of the European Study Group on the Molecular Biology of Picornaviruses, Lunteren, The Netherlands, 23-29th May 2005. Abstract A14.

Knowles, N.J., Hales, L.M., Jones, B.H., Landgraf, J.G., House, J.A., Skele, K.L., Burroughs, K.D. and Hallenbeck, P.L. (2006). Epidemiology of Seneca Valley virus: identification and characterization of isolates from pigs in the United States. Northern Lights EUROPIC 2006: XIV^th Meeting of the European Study Group on the Molecular Biology of Picornaviruses, Saariselkä, Inari, Finland, 26th November-1st December 2006. Abstract G2.

Reddy, P.S., Burroughs, K.D., Hales, L.M., Ganesh, S., Jones, B.H., Idamakanti, N., Hay, C., Li, S.S., Skele, K.L., Vasko, A.J., Yang, J., Watkins, D.N., Rudin, C.M. and Hallenbeck, P.L. (2007). Seneca Valley virus, a systemically deliverable oncolytic picornavirus, and the treatment of neuroendocrine cancers. J Natl Cancer Inst. 99: 1623-2633. Epub 2007 Oct 30.

Wadhwa, L., Hurwitz, M.Y., Chévez-Barrios, P. and Hurwitz, R.L. (2007). Treatment of invasive retinoblastoma in a murine model using an oncolytic picornavirus. Cancer Res. 67: 10653-10656.