Cryo-Electron Microscopy Structure of Seneca Valley Virus Procapsid

Abstract

Seneca Valley Virus, like some other members of the picornaviridae, forms naturally occurring empty capsids, known as procapsids. The procapsid has the same antigenicity as the full virion, so they present an interesting possibility for the formation of stable virus-like particles. Interestingly, although SVV is a livestock pathogen, it has also been found to preferentially infect tumour cells, and is being explored for use as a therapeutic agent in the treatment of small cell lung cancers. Here we used cryo-electron microscopy to investigate the procapsid structure and describe the transition of capsid protein VP0 to the cleaved forms of VP4 and VP2. We show that the SVV receptor binds the procapsid, as evidence of its native antigenicity. In comparing the procapsid structure to that of the full virion, we also show that a cage of RNA serves to stabilize the inside surface of the virus, thereby making it more acid-stable.Viruses are extensively studied to help us understand infection and disease. One of the by-products of some virus infections are the naturally occurring empty virus capsids (containing no genome), termed procapsids, whose function remains unclear. Here we investigate the structure and formation of the procapsids of Seneca Valley Virus, to better understand how they form, what causes them to form, how they behave, and how we can make use of them. One potential benefit of this work is the modification of the procapsid to develop it for targeted delivery of therapeutics or to make a stable vaccine against SVV, which could be of great interest to the agricultural industry.

Seneca Valley virus attachment and uncoating mediated by its receptor anthrax toxin receptor 1

“…Structures of mature SVV and the procapsid have been determined previously by crystallography and cryo-EM (19,20), and the binding of ANTXR1 to SVV has been visualized at low resolution (5,19). Structural comparison of the capsids suggests that SVV lies between aphthoviruses and cardioviruses, and is quite distant from enteroviruses (21).…”

Seneca Valley Virus Exploits TEM8, a Collagen Receptor Implicated in Tumor Growth

“…The exogenous expression of TEM8 in non-permissive H69 and H146 SCLC cells allowed for effective SVV entry and killing. TEM8, but not CMG2 was also shown to directly bind SVV via co-immunoprecipitation studies ( 6 ) and cryo-electron microscopy of SVV-TEM8 mixtures revealed a regular labeling of SVV's capsid with TEM8 molecules, confirming its status as the SVV receptor ( 53 ).…”

<p>Virus–Receptor Interactions: Structural Insights For Oncolytic Virus Development</p>

“…239 Furthermore, we showed that SVV binding site on ANTXR1 is non-conserved in its paralogous receptor, ANTXR2, which is expressed in normal cells, thereby providing a structural basis for tumor specificity of SVV. 240 SVV empty capsid binds ANTXR1, suggesting it may have potential as a vaccine or as virus-like particles for the development of tumor-targeted delivery of drugs. 240 As suggested from both functional and structural studies, the tumor tropism of SVV-001 is attributed to receptor-mediated internalization of the virus, a phenomenon common to other oncolytic picornaviruses.…”

“…240 SVV empty capsid binds ANTXR1, suggesting it may have potential as a vaccine or as virus-like particles for the development of tumor-targeted delivery of drugs. 240 As suggested from both functional and structural studies, the tumor tropism of SVV-001 is attributed to receptor-mediated internalization of the virus, a phenomenon common to other oncolytic picornaviruses. However, a successful SVV-001 infection may also require an additional innate immune defect.…”