Seneca Valley virus

Child level

Seneca Valley virus seqs

Same level

  Senaca Valley virus 1 (SVV-1) belongs to the species Senecavirus valles (formerly Senecavirus A) in the genus Senecavirus.

The complete genome sequence of Seneca Valley virus 1 (SVV-1) 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 P1cap (Fig. 1), 2C, 3Cpro and 3Dpol (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 NPGP 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culture contaminant, but has since been found in pigs throughout the United States (Knowles et al., 2006; Hales et al., unpublished data).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 of early (prior to 1997) virus isolates 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.

Seneca Valley virus 1 has been reported as the possible cause of idiopathic vesicular disease in pigs in the USA, Canada, Brazil and China (Pasma et al., 2008; Singh et al., 2012; Leme et al., 2015; Leme et al., 2016; Vannucci et al., 2015; Canning et al., 2016; Gimenez-Lirola et al., 2016; Guo et al., 2016; Hause et al., 2016; Joshi et al., 2016; Wang et al., 2016; Wu et al., 2016; Xu et al., 2017). SVV has now been reported in pigs in Colombia (Sun et al., 2017) and Thailand in 2016 (Saeng-Chuto et al., 2017) and Vietnam in 2018 (Bertram et al., unpub.).

Real-time RT-PCRs for diagnosis have been developed (Bracht et al., 2016; Fowler et al., 2017).

Recently, vesicular lesions have been produced in pigs following experimental infection with SVV (Montiel et al., 2016).

Anthrax toxin receptor 1 (ANTXR1) has identified as a cellular receptor for SVV-1 (Miles et al., 2017).

Genome organisation



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.

Bracht, A.J., O'Hearn, E.S., Fabian, A.W., Barrette, R.W. and Sayed, A. (2016). Real-time reverse transcription PCR assay for detection of Senecavirus A in swine vesicular diagnostic specimens. PLoS One 11(1): e0146211.

Canning, P., Canon, A., Bates, J.L., Gerardy, K., Linhares, D.C., Piñeyro, P.E., Schwartz, K.J., Yoon, K.J., Rademacher, C.J., Holtkamp, D. and Karriker, L. (2016). Neonatal mortality, vesicular lesions and lameness associated with Senecavirus A in a U.S. sow farm. Transbound. Emerg. Dis. 2016 May 23 [Epub ahead of print].

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.

Friedman, G.K., Cassady, K.A., Beierle, E.A., Markert, J.M. and Gillespie, G.Y. (2012). Targeting pediatric cancer stem cells with oncolytic virotherapy. Pediatr Res. 71: 500-510.

Fowler VL, Ransburgh RH, Poulsen EG, Wadsworth J, King DP, Mioulet V, Knowles NJ, Williamson S, Liu X, Anderson GA, Fang Y, Bai J. Development of a novel real-time RT-PCR assay to detect Seneca Valley virus-1 associated with emerging cases of vesicular disease in pigs. J Virol Methods. 2017 Jan;239:34-37. doi: 10.1016/j.jviromet.2016.10.012. Epub 2016 Oct 29. PubMed PMID: 27916668.

Gimenez-Lirola, L.G., Rademacher, C., Linhares, D., Harmon, K., Rotolo, M., Sun, Y., Baum, D.H., Zimmerman, J. and Piñeyro, P. (2016). Serological and molecular detection of Senecavirus A associated with an outbreak of swine idiopathic vesicular disease and neonatal mortality. J. Clin. Microbiol. 2016 May 25. pii: JCM.00710-16. [Epub ahead of print].

Guo, B., Piñeyro, P.E., Rademacher, C.J., Zheng, Y., Li, G., Yuan, J., Hoang, H., Gauger, P.C., Madson, D.M., Schwartz, K.J., Canning, P.E., Arruda, B.L., Cooper, V.L., Baum, D.H., Linhares, D.C., Main, R.G. and Yoon, K.J. (2016). Novel Senecavirus A in swine with vesicular disease, United States, July 2015. Emerg. Infect. Dis. 22: 1325-1327.

Hallenbeck, P.L., Reddy, S.P. and Ganesh, S. (2005). Abstract 725. Seneca Valley virus, a novel systemically deliverable oncolytic virus for the treatment of small cell lung cancer and other neuroendocrine cancers. Molecular Therapy 11: S281|[ndash]|S281; doi: 10.1016/j.ymthe.2005.07.265.

Hales, L.M., Jones, B.H., Vasko, A.-J., Knowles, N.J., Police, S.R. and Hallenbeck, P.L. (2006). 481. Epidemiology of Seneca Valley virus (SVV-001), a novel oncolytic picornavirus for the systemic treatment of patients with solid cancers with neuroendocrine features. Molecular Therapy 13: S187|[ndash]|S187; doi: 10.1016/j.ymthe.2006.08.550.

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 89: 1265-1275.

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.

Hause, B.M., Myers, O., Duff, J. and Hesse, R.A. (2016). Senecavirus A in pigs, United States, 2015. Emerg. Infect. Dis. 22: 1323-1325.

Hellen, C.U, 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. Epub 2007 Mar 28.

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.

Joshi, L.R., Mohr, K.A., Clement, T., Hain, K.S., Myers, B., Yaros, J., Nelson, E.A., Christopher-Hennings, J., Gava, D., Schaefer, R., Caron, L., Dee, S. and Diel, D.G. (2016). Detection of the emerging Senecavirus A in pigs, mice and houseflies. J. Clin. Microbiol. 2016 Mar 30. pii: JCM.03390-15 [Epub ahead of print].

Knowles, N.J. and Hallenbeck, P.L. (2005). A new picornavirus is most closely related to cardioviruses. EUROPIC 2005: XIIIth 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: XIVth Meeting of the European Study Group on the Molecular Biology of Picornaviruses, Saariselkä, Inari, Finland, 26th November-1st December 2006. Abstract G2.

Koppers-Lalic, D. and Hoeben, R.C. (2011). Non-human viruses developed as therapeutic agent for use in humans. Rev Med Virol. 21: 227-239. Epub 2011 May 11.

Leme, R.A., Zotti, E., Alcântara, B.K., Oliveira, M.V., Freitas, L.A., Alfieri, A.F., Alfieri, A.A. (2015). Senecavirus A: an emerging vesicular infection in Brazilian pig herds. Transbound. Emerg. Dis. 2015 Sep 23. doi: 10.1111/tbed.12430. [Epub ahead of print].

Leme, R.A., Oliveira, T.E., Alcântara, B.K., Headley, S.A., Alfieri, A.F., Yang, M. and Alfieri, A.A. (2016). Clinical manifestations of Senecavirus A infection in neonatal pigs, Brazil, 2015. Emerg. Infect. Dis. 22: 1238-1241.

Liu, Z., Zhao, X., Mao, H., Baxter, P.A., Huang, Y., Yu, L., Wadhwa, L., Su, J.M., Adesina, A., Perlaky, L., Hurwitz, M., Idamakanti, N., Police, S.R., Hallenbeck, P.L., Hurwitz, R.L., Lau, C.C., Chintagumpala, M., Blaney, S.M. and Li, X.N. (2013). Intravenous injection of oncolytic picornavirus SVV-001 prolongs animal survival in a panel of primary tumor-based orthotopic xenograft mouse models of pediatric glioma. Neuro. Oncol. 2013 May 7 [Epub ahead of print].

Miles, L.A., Burga, L.N., Gardner, E.E., Bostina, M., Poirier, J.T. and Rudin, C.M. (2017). Anthrax toxin receptor 1 is the cellular receptor for Seneca Valley virus. J. Clin. Invest. 2017 Jun 26. pii: 93472. doi: 10.1172/JCI93472. [Epub ahead of print]

Montiel, N., Buckley, A., Guo, B., Kulshreshtha, V., VanGeelen, A., Hoang, H., Rademacher, C., Yoon, K.J. and Lager, K. (2016). Vesicular disease in 9-week-old pigs experimentally infected with Senecavirus A. Emerg. Infect. Dis. 22: 1246-1248.

Morton, C.L., Houghton, P.J., Kolb, E.A., Gorlick, R., Reynolds, C.P., Kang, M.H., Maris, J.M., Keir, S.T., Wu, J. and Smith, M.A. (2010). Initial testing of the replication competent Seneca Valley virus (NTX-010) by the pediatric preclinical testing program. Pediatr. Blood Cancer. 55: 295-303. Erratum in: Pediatr Blood Cancer. 2012 Apr;58(4):652.

Pasma, T., Davidson, S. and Shaw, S.L. (2008). Idiopathic vesicular disease in swine in Manitoba. Can Vet. J. 49: 84–85.

Poirier, J.T., Reddy, P.S., Idamakanti, N., Li, S.S., Stump, K.L., Burroughs, K.D., Hallenbeck, P.L. and Rudin, C.M. (2012). Characterization of a full-length infectious cDNA clone and a green fluorescent protein reporter derivative of the oncolytic picornavirus SVV-001. J. Gen. Virol. 2012 Sep 12. [Epub ahead of print]

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: 1623-1633. Epub 2007 Oct 30.

Rudin, C.M., Poirier, J.T., Senzer, N.N., Stephenson, J. Jr., Loesch, D., Burroughs, K.D., Reddy, P.S., Hann, C.L. and Hallenbeck, P.L. (2011). Phase I clinical study of Seneca Valley Virus (SVV-001), a replication-competent picornavirus, in advanced solid tumors with neuroendocrine features. Clin Cancer Res. 17: 888-895. Epub 2011 Feb 8.

Saeng-Chuto, K., Rodtian, P., Temeeyasen, G., Wegner, M. and Nilubol, D. (2017). The first detection of Senecavirus A in pigs in Thailand, 2016. Transbound. Emerg. Dis. 2017 May 5. doi: 10.1111/tbed.12654. [Epub ahead of print]

Singh, K., Corner, S., Clark, S.G., Scherba, G. and Fredrickson, R. (2012). Seneca Valley virus and vesicular lesions in a pig with idiopathic vesicular disease. J. Vet. Sci. Technol. 3: 123 doi:10.4172/2157-7579.1000123.

Sun, D., Vannucci, F., Knutson, T.P., Corzo, C. and Marthaler, D.G. (2017). Emergence and whole-genome sequence of Senecavirus A in Colombia. Transbound. Emerg. Dis. 2017 Jul 16. doi: 10.1111/tbed.12669. [Epub ahead of print]

Vannucci, F.A., Linhares, D.C., Barcellos, D.E., Lam, H.C., Collins, J. and Marthaler, D. (2015). Identification and complete genome of Seneca Valley Virus in vesicular fluid and sera of pigs affected with idiopathic vesicular disease, Brazil. Transbound. Emerg. Dis. 2015 Sep 7. doi: 10.1111/tbed.12410. [Epub ahead of print].

Venkataraman, S., Reddy, S.P., Loo, J., Idamakanti, N., Hallenbeck, P.L. and Reddy, V.S. (2008). Crystallization and preliminary X-ray diffraction studies of Seneca Valley Virus-001, a new member of the Picornaviridae family. Acta Crystallographica Section F: Structural Biology and Crystallization Communications 64: 293-296.

Venkataraman, S., Reddy, S.P., Loo, J., Idamakanti, N., Hallenbeck, P.L. and Reddy, V.S. (2008). Structure of Seneca Valley virus-001: an oncolytic picornavirus representing a new genus. Structure 16: 1555-1561.

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.

Wang, L., Prarat, M., Hayes, J. and Zhang, Y. (2016). Detection and genomic characterization of Senecavirus A, Ohio, USA, 2015. Emerg. Infect. Dis. 22: 1321-1323.

Willcocks, M.M., Locker, N., Gomwalk, Z., Royall, E., Bakhshesh, M., Belsham, G.J., Idamakanti, N., Burroughs, K.D., Reddy, P.S., Hallenbeck, P.L. and Roberts, L.O. (2011). Structural features of the Seneca Valley virus internal ribosome entry site (IRES) element: a picornavirus with a pestivirus-like IRES. J. Virol. 85: 4452-4461. Epub 2011 Feb 16.

Wu, Q., Zhao, X., Chen, Y., He, X., Zhang, G. and Ma, J. (2016). Complete genome sequence of Seneca Valley virus CH-01-2015 identified in China. Genome Announc. 4(1). pii: e01509-15.

Xu, W., Hole, K., Goolia, M., Pickering, B., Salo, T., Lung, O. and Nfon, C. (2017). Genome wide analysis of the evolution of Senecavirus A from swine clinical material and assembly yard environmental samples. PLoS One. 2017 May 5;12(5):e0176964. doi: 10.1371/journal.pone.0176964. eCollection 2017.

Yang, M., van Bruggen, R. and Xu, W. (2012). Generation and diagnostic application of monoclonal antibodies against Seneca Valley virus. J. Vet. Diagn. Invest. 24: 42-50. Epub 2011 Dec 6.

Yu, L., Baxter, P.A., Zhao, X., Liu, Z., Wadhwa, L., Zhang, Y., Su, J.M., Tan, X., Yang, J., Adesina, A., Perlaky, L., Hurwitz, M., Idamakanti, N., Police, S.R., Hallenbeck, P.L., Blaney, S.M., Chintagumpala, M., Hurwitz, R.L. and Li, X.N. (2010). A single intravenous injection of oncolytic picornavirus SVV-001 eliminates medulloblastomas in primary tumor-based orthotopic xenograft mouse models. Neuro Oncol. 2010 Nov 12. [Epub ahead of print].



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