Syncytia Formation Promotes Virus Resistance to Interferon and Neutralizing Antibodies

Syncytia Formation Promotes Virus Resistance to Interferon and Neutralizing Antibodies | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Biological Sciences - Article Syncytia Formation Promotes Virus Resistance to Interferon and Neutralizing Antibodies Jon W. Yewdell, Tiansheng Li, Insung Kang, Zhe Hu, James Gibbs, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3846435/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract SARS-CoV-2, like many viruses, generates syncytia. Using SARS-CoV-2 and Spike (S) expressing recombinant vesicular stomatitis and influenza A viruses, we show that S-mediated syncytia formation provides resistance to interferons in cultured cells, human small airway-derived air-liquid interface cultures and hACE2 transgenic mice. Amino acid substitutions that modulate fusogenicity in Delta- and Omicron-derived S have parallel effects on viral interferon resistance. Syncytia formation also decreases antibody virus neutralization activity in cultured cells. These findings explain the continued selection of fusogenic variants during SARS-CoV-2 evolution in humans and, more generally, the evolution of fusogenic viruses despite the adverse effects of syncytia formation on viral replication in the absence of innate or adaptive immune pressure. Biological sciences/Microbiology/Virology/SARS-CoV-2 Biological sciences/Microbiology/Virology/Viral immune evasion Full Text Additional Declarations There is NO Competing Interest. Supplementary Files Video1rVSVSWTNonIFN.mp4 VSV-S wt infection in Vero cells without IFN-β treatment Video2rVSVSWTIFNbeta.mp4 VSV-S wt infection in Vero cells with IFN-β treatment Video3rVSVSR685SNonIFN.mp4 VSV-S R685S infection in Vero cells without IFN-β treatment Video4rVSVSR685SIFNbeta.mp4 VSV-S R685S infection in Vero cells with IFN-β treatment Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3846435","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Biological Sciences - Article","associatedPublications":[],"authors":[{"id":270131526,"identity":"d766027c-fd0e-48be-9447-eb4cc9dcc06c","order_by":0,"name":"Jon W. 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Using SARS-CoV-2 and Spike (S) expressing recombinant vesicular stomatitis and influenza A viruses, we show that S-mediated syncytia formation provides resistance to interferons in cultured cells, human small airway-derived air-liquid interface cultures and hACE2 transgenic mice. Amino acid substitutions that modulate fusogenicity in Delta- and Omicron-derived S have parallel effects on viral interferon resistance. Syncytia formation also decreases antibody virus neutralization activity in cultured cells. 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