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Picornaviruses: A View from 3A
Communication

N-Linked Glycosylation on Anthrax Toxin Receptor 1 Is Essential for Seneca Valley Virus Infection

1
Department of Microbiology and Immunology, University of Otago, Dunedin 9016, New Zealand
2
Molecular Cryo-Electron Microscopy Unit, Okinawa Institute of Science and Technology Graduate University, Onna-son, Okinawa 904-0495, Japan
3
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
4
Druckenmiller Center for Lung Cancer Research and Department of Medicine, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
5
Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan
6
Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, NY 10016, USA
7
Otago Micro and Nano Imaging Centre, University of Otago, Dunedin 9016, New Zealand
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Caroline Tapparel
Viruses 2021, 13(5), 769; https://doi.org/10.3390/v13050769
Received: 29 March 2021 / Revised: 22 April 2021 / Accepted: 25 April 2021 / Published: 28 April 2021
(This article belongs to the Special Issue Picornaviruses)
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. View Full-Text
Keywords: virus receptor interaction; receptor glycosylation; picornavirus; icosahedral capsid; cryo-electron microscopy virus receptor interaction; receptor glycosylation; picornavirus; icosahedral capsid; cryo-electron microscopy
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MDPI and ACS Style

Jayawardena, N.; Miles, L.A.; Burga, L.N.; Rudin, C.; Wolf, M.; Poirier, J.T.; Bostina, M. N-Linked Glycosylation on Anthrax Toxin Receptor 1 Is Essential for Seneca Valley Virus Infection. Viruses 2021, 13, 769. https://doi.org/10.3390/v13050769

AMA Style

Jayawardena N, Miles LA, Burga LN, Rudin C, Wolf M, Poirier JT, Bostina M. N-Linked Glycosylation on Anthrax Toxin Receptor 1 Is Essential for Seneca Valley Virus Infection. Viruses. 2021; 13(5):769. https://doi.org/10.3390/v13050769

Chicago/Turabian Style

Jayawardena, Nadishka, Linde A. Miles, Laura N. Burga, Charles Rudin, Matthias Wolf, John T. Poirier, and Mihnea Bostina. 2021. "N-Linked Glycosylation on Anthrax Toxin Receptor 1 Is Essential for Seneca Valley Virus Infection" Viruses 13, no. 5: 769. https://doi.org/10.3390/v13050769

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