Senecavirus Explained

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 only one species in this genus: 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.It has potential antineoplastic activity.[4] [5]

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.

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.

The receptor for Seneca Valley virus has been identified as anthrax toxin receptor 1.[6]

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]

While the sequence of SVV's protein-coding genome is most similar to members in the Cardiovirus genus, the non-coding RNA internal ribosome entry site (IRES) is most similar to those of the Pestivirus genus, including classical swine fever virus, and Hepacivirus genus, including Hepatitis C virus.[11]

The SVV IRES RNA shares similarities in sequence, structure, and function with the hepatitis C virus IRES. Subdomain IIa of the SVV and HCV IRES shares a similar structure and ligand-binding function as seen in its crystal structure.[12] This subdomain IIa region is classified as a ligand-responsive RNA switch which adopts well-defined ligand-free and bound conformations without breaking or forming any base pairs in its secondary structure upon interconversion between the two states.[13] This RNA switch from the SVV IRES has been incorporated into triangular RNA nanostructures.[14]

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

Senecavirus uses the anthrax toxin receptor 1 (ANTXR1) protein as a receptor.[19] A high-resolution structure of senecavirus with this receptor has been published.[20]

See also

External links

Notes and References

  1. Web site: Viral Zone. ExPASy. 15 June 2015.
  2. Web site: Virus Taxonomy: 2020 Release . International Committee on Taxonomy of Viruses (ICTV) . March 2021 . 20 May 2021.
  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. 10.1093/jnci/djm198 . A. -J.. Yang . J.. Watkins . D. N.. Rudin . C. M.. Hallenbeck . P. L.. 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. 2007. 17971529. 5261858.
  4. National Cancer Institute Definition of Seneca Valley virus-001. National Cancer Institute Retrieved on 2008-10-09.
  5. Morton CL, Houghton PJ, Kolb EA, etal . Initial testing of the replication competent Seneca Valley virus (NTX-010) by the pediatric preclinical testing program . Pediatr Blood Cancer . 55 . 2 . 295–303 . August 2010 . 20582972 . 10.1002/pbc.22535 . 3003870 .
  6. Miles LA, Burga LN, Gardner EE, Bostina M, Poirier JT, Rudin CM (2017) Anthrax toxin receptor 1 is the cellular receptor for Seneca Valley virus. J Clin Invest
  7. Hales . L. M.. Knowles . N. J.. Reddy . P. S.. Xu . L.. Hay . C.. Hallenbeck . P. L.. 10.1099/vir.0.83570-0. Complete genome sequence analysis of Seneca Valley virus-001, a novel oncolytic picornavirus. Journal of General Virology. 89. 5. 1265–1275. 2008. 18420805. free.
  8. Poirier . J. T.. Reddy . P. S.. Idamakanti . N.. Li . S. S.. Stump . K. L.. Burroughs . K. D.. Hallenbeck . P. L.. Rudin . C. M.. 10.1099/vir.0.046011-0. 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. 2012. 22971818. free.
  9. Friedman . G. K.. Cassady . K. A.. Beierle . E. A.. Markert . J. M.. Gillespie . G. Y.. Targeting pediatric cancer stem cells with oncolytic virotherapy. 10.1038/pr.2011.58. Pediatric Research. 71. 4–2. 500–510. 2012. 22430386. 3607376.
  10. Yang . M.. Van Bruggen . R.. Xu . W.. 10.1177/1040638711426323. Generation and diagnostic application of monoclonal antibodies against Seneca Valley virus. Journal of Veterinary Diagnostic Investigation. 24. 1. 42–50. 2011. 22362934. free.
  11. Willcocks . M. M.. Locker . N.. Gomwalk . Z.. Royall . E.. Bakhshesh . M.. Belsham . G. J.. Idamakanti . N.. Burroughs . K. D.. Reddy . P. S.. Hallenbeck. 10.1128/JVI.01107-10 . P. L.. Roberts . L. O.. 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. 2011. 21325406. 3126232.
  12. Boerneke. Mark. Dibrov. Sergey. Gu. Jing. Wyles. David. Hermann. Thomas. Functional conservation despite structural divergence in ligand-responsive RNA switches. Proc Natl Acad Sci U S A. November 11, 2014. 111. 45. 10.1073/pnas.1414678111. 25349403. 4234586. 15952–7. 2014PNAS..11115952B. free.
  13. Boerneke. Mark. Hermann. Thomas. Ligand-responsive RNA mechanical switches. RNA Biology. August 2015. 12. 8. 780–786. 10.1080/15476286.2015.1054592. 26158858. 4615790.
  14. Boerneke. Mark. Dibrov. Sergey. Hermann. Thomas. Crystal-Structure-Guided Design of Self-Assembling RNA Nanotriangles. Angew Chem Int Ed Engl. February 23, 2016. 55. 12. 10.1002/anie.201600233. 26914842. 4097–100. 4824544.
  15. Web site: Safety Study of Seneca Valley Virus in Patients With Solid Tumors With Neuroendocrine Features . 23 February 2010 . ClinicalTrials.gov.
  16. Rudin CM, Poirier JT, Senzer NN, Stephenson J, Loesch D, Burroughs KD, Reddy PS, Hann CL, Hallenbeck PL . Phase I clinical study of Seneca Valley Virus (SVV-001), a replication-competent picornavirus, in advanced solid tumors with neuroendocrine features . Clinical Cancer Research . February 15, 2011 . 17 . 4 . 888–95 . 10.1158/1078-0432.CCR-10-1706 . 21304001 . 5317273.
  17. Web site: Seneca Valley Virus-001 After Chemotherapy in Treating Patients With Extensive-Stage Small Cell Lung Cancer . clinicaltrials.gov.
  18. Web site: Seneca Valley Virus-001 and Cyclophosphamide in Treating Young Patients With Relapsed or Refractory Neuroblastoma, Rhabdomyosarcoma, or Rare Tumors With Neuroendocrine Features . clinicaltrials.gov.
  19. Miles . LA . Burga . LN . Gardner . EE . Bostina . M . Poirier . JT . Rudin . CM . Anthrax toxin receptor 1 is the cellular receptor for Seneca Valley virus. . The Journal of Clinical Investigation . 1 August 2017 . 127 . 8 . 2957–2967 . 10.1172/JCI93472 . 28650343. 5531414 . free .
  20. Jayawardena . N . Burga . LN . Easingwood . RA . Takizawa . Y . Wolf . M . Bostina . M . Structural basis for anthrax toxin receptor 1 recognition by Seneca Valley Virus. . Proceedings of the National Academy of Sciences of the United States of America . 13 November 2018 . 115 . 46 . E10934–E10940 . 10.1073/pnas.1810664115 . 30381454. 6243253 . free . 2018PNAS..11510934J .

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