Senecavirus

Senecavirus
Virus classification
Group: Group IV ((+)ssRNA)
Order: Picornavirales
Family: Picornaviridae
Genus: Senecavirus
Type species
Senecavirus A
Synonyms
  • Seneca Valley virus
  • Seneca Valley virus-001

Senecavirus is a genus of viruses in the order Picornavirales, in the family Picornaviridae. Pig and maybe also cow serve as natural hosts. There is currently only one species in this genus: the type species Senecavirus A.'[1][2] Senecavirus is a replication-competent oncolytic picornavirus. It has selective tropism for cancers with neuroendocrine features including small cell lung cancer (SCLC) and several pediatric solid tumors including retinoblastoma, neuroblastoma, and medulloblastoma.[3] A Phase I clinical trial of Senecavirus in adults with neuroendocrine tumors showed that senecavirus is apparently safe to administer at doses up to 1E11 vp/kg.[4]

It has potential antineoplastic activity.[5][6]

Structure

Viruses in Senecavirus are non-enveloped, with icosahedral, spherical, and round geometries, with T=pseudo3 symmetry. The diameter is around 30 nm. Genomes are linear and non-segmented, around 7.3kb in length.[1]

Genus Structure Symmetry Capsid Genomic Arrangement Genomic Segmentation
SenecavirusIcosahedralPseudo T=3Non-EnvelopedLinearMonopartite

Life Cycle

Viral replication is cytoplasmic. Entry into the host cell is achieved by attachment of the virus to host receptors, which mediates endocytosis. Replication follows the positive stranded RNA virus replication model. Positive stranded RNA virus transcription is the method of transcription. The virus exits the host cell by lysis, and viroporins. Pig and maybe also cow serve as the natural host.[1]

Genus Host Details Tissue Tropism Entry Details Release Details Replication Site Assembly Site Transmission
SenecavirusPigs, CowOncolyticCell receptor endocytosisLysisCytoplasmCytoplasmUnknown

Taxonomy

Group: ssRNA(+)

[2]

Discovery and origin

The complete genome sequence of senecavirus was completed in 2008.[7]

An infectious clone of senecavirus was reported in 2012.[8]

Senecavirus has been proposed to attack cancer stem cells.[9]

Diagnostic monoclonal antibodies have been generated against senecavirus.[10]

It has been suggested that not enough safety information is yet available. This determination was made prior to results of the phase I clinical trial being published.[11]

While the sequence of SVV proteins is most similar to cardioviruses, the non-coding internal ribosomal entry site (IRES) is most similar to those of pestviruses including classical swine fever virus.[12]

Clinical trials

The initial isolate is being developed as an anti-cancer therapeutic by virtual company Neotropix, Inc. under the name NTX-010.

Phase I

Phase II

Virus replication

It is believed that senecavirus internalizes by receptor-mediated internalization, but as yet no host receptor has been identified.

See also

References

  1. 1 2 3 "Viral Zone". ExPASy. Retrieved 15 June 2015.
  2. 1 2 ICTV. "Virus Taxonomy: 2014 Release". Retrieved 15 June 2015.
  3. ↑ 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.; Hallenbeck, P. L. (2007). "Seneca Valley Virus, a Systemically Deliverable Oncolytic Picornavirus, and the Treatment of Neuroendocrine Cancers". JNCI Journal of the National Cancer Institute 99 (21): 1623–1633. doi:10.1093/jnci/djm198. PMID 17971529.
  4. ↑ Rudin, C. M.; Poirier, J. T.; Senzer, N. N.; Stephenson Jr, J.; Loesch, D.; Burroughs, K. D.; Reddy, P. S.; Hann, C. L.; 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". Clinical Cancer Research 17 (4): 888–895. doi:10.1158/1078-0432.CCR-10-1706. PMID 21304001.
  5. ↑ National Cancer Institute Definition of Seneca Valley virus-001. National Cancer Institute Retrieved on 2008-10-09.
  6. ↑ Morton CL, Houghton PJ, Kolb EA, et al. (August 2010). "Initial testing of the replication competent Seneca Valley virus (NTX-010) by the pediatric preclinical testing program". Pediatr Blood Cancer 55 (2): 295–303. doi:10.1002/pbc.22535. PMC 3003870. PMID 20582972.
  7. ↑ Hales, L. M.; Knowles, N. J.; Reddy, P. S.; Xu, L.; Hay, C.; Hallenbeck, P. L. (2008). "Complete genome sequence analysis of Seneca Valley virus-001, a novel oncolytic picornavirus". Journal of General Virology 89 (5): 1265–1275. doi:10.1099/vir.0.83570-0. PMID 18420805.
  8. ↑ Poirier, J. T.; Reddy, P. S.; Idamakanti, N.; Li, S. S.; Stump, K. L.; Burroughs, K. D.; Hallenbeck, P. L.; Rudin, C. M. (2012). "Characterization of a full-length infectious cDNA clone and a GFP reporter derivative of the oncolytic picornavirus SVV-001". Journal of General Virology 93 (Pt 12): 2606–2613. doi:10.1099/vir.0.046011-0. PMID 22971818.
  9. ↑ Friedman, G. K.; Cassady, K. A.; Beierle, E. A.; Markert, J. M.; Gillespie, G. Y. (2012). "Targeting pediatric cancer stem cells with oncolytic virotherapy". Pediatric Research 71 (4–2): 500–510. doi:10.1038/pr.2011.58. PMID 22430386.
  10. ↑ Yang, M.; Van Bruggen, R.; Xu, W. (2011). "Generation and diagnostic application of monoclonal antibodies against Seneca Valley virus". Journal of Veterinary Diagnostic Investigation 24 (1): 42–50. doi:10.1177/1040638711426323. PMID 22362934.
  11. ↑ Koppers-Lalic, D.; Hoeben, R. C. (2011). "Non-human viruses developed as therapeutic agent for use in humans". Reviews in Medical Virology 21 (4): 227–239. doi:10.1002/rmv.694. PMID 21560181.
  12. ↑ 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.; Roberts, L. O. (2011). "Structural Features of the Seneca Valley Virus Internal Ribosome Entry Site (IRES) Element: A Picornavirus with a Pestivirus-Like IRES". Journal of Virology 85 (9): 4452–4461. doi:10.1128/JVI.01107-10. PMC 3126232. PMID 21325406.
  13. ↑ "Safety Study of Seneca Valley Virus in Patients With Solid Tumors With Neuroendocrine Features".
  14. ↑ Rudin, CM; Poirier, JT; Senzer, NN; Stephenson J, Jr; Loesch, D; Burroughs, KD; Reddy, PS; Hann, CL; Hallenbeck, PL (Feb 15, 2011). "Phase I clinical study of Seneca Valley Virus (SVV-001), a replication-competent picornavirus, in advanced solid tumors with neuroendocrine features". Clinical cancer research : an official journal of the American Association for Cancer Research 17 (4): 888–95. doi:10.1158/1078-0432.CCR-10-1706. PMID 21304001. Retrieved 30 May 2013. Cite uses deprecated parameter |coauthors= (help)
  15. ↑ "Seneca Valley Virus-001 After Chemotherapy in Treating Patients With Extensive-Stage Small Cell Lung Cancer".
  16. ↑ "Seneca Valley Virus-001 and Cyclophosphamide in Treating Young Patients With Relapsed or Refractory Neuroblastoma, Rhabdomyosarcoma, or Rare Tumors With Neuroendocrine Features".

External links

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