''Senecavirus'' is a genus of

viruses A virus is a submicroscopic infectious agent that replicates only inside the living cells Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room ...

in the order ''

Picornavirales ''Picornavirales'' is an order of viruses with vertebrate, invertebrate, protist and plant hosts. The name has a dual etymology. First, ''picorna-'' is an acronym for poliovirus, insensitivity to ether, coxsackievirus, orphan virus, rhinovirus ...

'', in the family ''

Picornaviridae Picornaviruses are a group of related nonenveloped RNA viruses which infect vertebrates including fish, mammals, and birds. They are viruses that represent a large family of small, positive-sense, single-stranded RNA viruses with a 30 ...

''. Pig and maybe also cow serve as natural hosts. There is only one species in this genus: ''Senecavirus A''. ''Senecavirus'' is a replication-competent oncolytic

picornavirus Picornaviruses are a group of related nonenveloped RNA viruses which infect vertebrates including fish, mammals, and birds. They are viruses that represent a large family of small, positive-sense, single-stranded RNA viruses with a 30 nm ...

. 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. 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.

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.

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.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

Discovery and origin

The complete genome sequence of senecavirus was completed in 2008. An infectious clone of senecavirus was reported in 2012. Senecavirus has been proposed to attack cancer stem cells. Diagnostic monoclonal antibodies have been generated against senecavirus. 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 An internal ribosome entry site, abbreviated IRES, is an RNA element that allows for translation initiation in a cap-independent manner, as part of the greater process of protein synthesis. In eukaryotic translation, initiation typically occurs at ...

(IRES) is most similar to those of the Pestivirus genus, including classical swine fever virus, and Hepacivirus genus, including

Hepatitis C virus The hepatitis C virus (HCV) is a small (55–65 nm in size), enveloped, positive-sense single-stranded RNA virus of the family '' Flaviviridae''. The hepatitis C virus is the cause of hepatitis C and some cancers such as liver cancer (hepatoc ...

. 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. 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. This RNA switch from the SVV IRES has been incorporated into triangular RNA nanostructures.

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 * Safety study of senecavirus in patients with solid tumors with neuroendocrine features. This study was published in 2011 and the data show that the virus was well tolerated by 30 patients and some signs of anti-tumour activity were observed. The data warranted further investigation of the virus in a phase II trial in

small cell lung cancer Small-cell carcinoma is a type of highly malignant cancer that most commonly arises within the lung, although it can occasionally arise in other body sites, such as the cervix, prostate, and gastrointestinal tract. Compared to non-small cell ca ...

. Phase II * Senecavirus after chemotherapy in treating patients with extensive-stage

* Senecavirus and cyclophosphamide in young patients with

neuroblastoma Neuroblastoma (NB) is a type of cancer that forms in certain types of nerve tissue. It most frequently starts from one of the adrenal glands but can also develop in the neck, chest, abdomen, or spine. Symptoms may include bone pain, a lump i ...

rhabdomyosarcoma Rhabdomyosarcoma (RMS) is a highly aggressive form of cancer that develops from mesenchymal cells that have failed to fully differentiate into myocytes of skeletal muscle. Cells of the tumor are identified as rhabdomyoblasts. There are four subty ...

, or rare tumors with neuroendocrine features

Virus replication

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

References

External links

Structure of Seneca Valley Virus-001
— on Virus Particle ExploreR (VIPERdb)

ICTV
{{DEFAULTSORT:Senecavirus Picornaviridae Virotherapy Virus genera