This page has only limited features, please log in for full access.
Seneca Valley virus (SVV) is a picornavirus with potency in selectively infecting and lysing cancerous cells. The cellular receptor for SVV mediating the selective tropism for tumors is anthrax toxin receptor 1 (ANTXR1), a type I transmembrane protein expressed in tumors. Similar to other mammalian receptors, ANTXR1 has been shown to harbor N-linked glycosylation sites in its extracellular vWA domain. However, the exact role of ANTXR1 glycosylation on SVV attachment and cellular entry was unknown. Here we show that N-linked glycosylation in the ANTXR1 vWA domain is necessary for SVV attachment and entry. In our study, tandem mass spectrometry analysis of recombinant ANTXR1-Fc revealed the presence of complex glycans at N166, N184 in the vWA domain, and N81 in the Fc domain. Symmetry-expanded cryo-EM reconstruction of SVV-ANTXR1-Fc further validated the presence of N166 and N184 in the vWA domain. Cell blocking, co-immunoprecipitation, and plaque formation assays confirmed that deglycosylation of ANTXR1 prevents SVV attachment and subsequent entry. Overall, our results identified N-glycosylation in ANTXR1 as a necessary post-translational modification for establishing stable interactions with SVV. We anticipate our findings will aid in selecting patients for future cancer therapeutics, where screening for both ANTXR1 and its glycosylation could lead to an improved outcome from SVV therapy.
Nadishka Jayawardena; Linde Miles; Laura Burga; Charles Rudin; Matthias Wolf; John Poirier; Mihnea Bostina. N-Linked Glycosylation on Anthrax Toxin Receptor 1 Is Essential for Seneca Valley Virus Infection. Viruses 2021, 13, 769 .
AMA StyleNadishka Jayawardena, Linde Miles, Laura Burga, Charles Rudin, Matthias Wolf, John Poirier, Mihnea Bostina. N-Linked Glycosylation on Anthrax Toxin Receptor 1 Is Essential for Seneca Valley Virus Infection. Viruses. 2021; 13 (5):769.
Chicago/Turabian StyleNadishka Jayawardena; Linde Miles; Laura Burga; Charles Rudin; Matthias Wolf; John Poirier; Mihnea Bostina. 2021. "N-Linked Glycosylation on Anthrax Toxin Receptor 1 Is Essential for Seneca Valley Virus Infection." Viruses 13, no. 5: 769.
Oncolytic viruses (OVs) are replication competent agents that selectively target cancer cells. After penetrating the tumor cell, viruses replicate and eventually trigger cell lysis, releasing the new viral progeny, which at their turn will attack and kill neighbouring cells. The ability of OVs to self-amplify within the tumor while sparing normal cells can provide several advantages including the capacity to encode and locally produce therapeutic protein payloads, and to prime the host immune system. OVs targeting of cancer cells is mediated by host factors that are differentially expressed between normal tissue and tumors, including viral receptors and internalization factors. In this review article, we will discuss the evolution of oncolytic viruses that have reached the stage of clinical trials, their mechanisms of oncolysis, cellular receptors, strategies for targeting cancers, viral neutralization and developments to bypass virus neutralization.
Nadishka Jayawardena; John T Poirier; Laura N Burga; Mihnea Bostina. Virus–Receptor Interactions and Virus Neutralization: Insights for Oncolytic Virus Development. Oncolytic Virotherapy 2020, ume 9, 1 -15.
AMA StyleNadishka Jayawardena, John T Poirier, Laura N Burga, Mihnea Bostina. Virus–Receptor Interactions and Virus Neutralization: Insights for Oncolytic Virus Development. Oncolytic Virotherapy. 2020; ume 9 ():1-15.
Chicago/Turabian StyleNadishka Jayawardena; John T Poirier; Laura N Burga; Mihnea Bostina. 2020. "Virus–Receptor Interactions and Virus Neutralization: Insights for Oncolytic Virus Development." Oncolytic Virotherapy ume 9, no. : 1-15.
The authors wish to make the following corrections to this paper
Cormac McCarthy; Nadishka Jayawardena; Laura N. Burga; Mihnea Bostina. Correction: McCarthy, C.; et al. Developing Picornaviruses for Cancer Therapy. Cancers 2019, 11, 685. Cancers 2020, 12, 553 .
AMA StyleCormac McCarthy, Nadishka Jayawardena, Laura N. Burga, Mihnea Bostina. Correction: McCarthy, C.; et al. Developing Picornaviruses for Cancer Therapy. Cancers 2019, 11, 685. Cancers. 2020; 12 (3):553.
Chicago/Turabian StyleCormac McCarthy; Nadishka Jayawardena; Laura N. Burga; Mihnea Bostina. 2020. "Correction: McCarthy, C.; et al. Developing Picornaviruses for Cancer Therapy. Cancers 2019, 11, 685." Cancers 12, no. 3: 553.
Oncolytic viruses (OVs) form a group of novel anticancer therapeutic agents which selectively infect and lyse cancer cells. Members of several viral families, including Picornaviridae, have been shown to have anticancer activity. Picornaviruses are small icosahedral non-enveloped, positive-sense, single-stranded RNA viruses infecting a wide range of hosts. They possess several advantages for development for cancer therapy: Their genomes do not integrate into host chromosomes, do not encode oncogenes, and are easily manipulated as cDNA. This review focuses on the picornaviruses investigated for anticancer potential and the mechanisms that underpin this specificity.
Cormac McCarthy; Nadishka Jayawardena; Laura N. Burga; Mihnea Bostina. Developing Picornaviruses for Cancer Therapy. Cancers 2019, 11, 685 .
AMA StyleCormac McCarthy, Nadishka Jayawardena, Laura N. Burga, Mihnea Bostina. Developing Picornaviruses for Cancer Therapy. Cancers. 2019; 11 (5):685.
Chicago/Turabian StyleCormac McCarthy; Nadishka Jayawardena; Laura N. Burga; Mihnea Bostina. 2019. "Developing Picornaviruses for Cancer Therapy." Cancers 11, no. 5: 685.
Seneca Valley virus (SVV), like some other members of the Picornaviridae , forms naturally occurring empty capsids, known as procapsids. Procapsids have the same antigenicity as full virions, 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 tumor 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. IMPORTANCE 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 in vivo delivery of therapeutics or to make a stable vaccine against SVV, which could be of great interest to the agricultural industry.
Mike Strauss; Nadishka Jayawardena; Eileen Sun; Richard A. Easingwood; Laura N. Burga; Mihnea Bostina. Cryo-Electron Microscopy Structure of Seneca Valley Virus Procapsid. Journal of Virology 2018, 92, e01927-17 .
AMA StyleMike Strauss, Nadishka Jayawardena, Eileen Sun, Richard A. Easingwood, Laura N. Burga, Mihnea Bostina. Cryo-Electron Microscopy Structure of Seneca Valley Virus Procapsid. Journal of Virology. 2018; 92 (6):e01927-17.
Chicago/Turabian StyleMike Strauss; Nadishka Jayawardena; Eileen Sun; Richard A. Easingwood; Laura N. Burga; Mihnea Bostina. 2018. "Cryo-Electron Microscopy Structure of Seneca Valley Virus Procapsid." Journal of Virology 92, no. 6: e01927-17.