The proviral factor NUP153 binds viral proteins and RNA to modulate protein translation at viral amplification site early in flavivirus infection

The proviral factor NUP153 binds viral proteins and RNA to modulate protein translation at viral amplification site early in flavivirus infection | 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 Article The proviral factor NUP153 binds viral proteins and RNA to modulate protein translation at viral amplification site early in flavivirus infection Anna Överby, Marie Peters, Richard Lindqvist, Eszter Kassa, Wai-Lok Yau, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4693768/v2 This work is licensed under a CC BY 4.0 License Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Abstract Orthoflaviviruses are RNA viruses that cause serious diseases in humans, with currently no antivirals available. Targeting host factors is emerging as an attractive antiviral approach. However, as a first step, there is a need to understand which host proteins are hijacked and for what purpose. Here, using a combination of fluorescence microscopy, knock-down, crosslinking immunoprecipitation sequencing, mass spectrometry, and in vitro and biophysical assays, we identify nucleoporin-153 (NUP153) as a proviral factor during orthoflavivirus infection. We show that NUP153 is recruited to the virus amplification site on the endoplasmic reticulum to regulate differential expression of specific viral proteins. We find that NUP153 interacts with both the viral proteins NS3 and NS5, and a highly conserved G-rich motif on the viral RNA. These interactions specificallypromote the production of viral structural proteins, leading to an efficient virion assembly, virus release and spread to new cells. We propose that NUP153 acts as a key regulator in viral polyprotein translation, a mechanism that appears conserved among orthoflaviviruses. Biological sciences/Microbiology/Virology/Virus–host interactions Biological sciences/Microbiology/Virology/West nile virus Full Text Additional Declarations The authors declare no competing interests. Supplementary Files Supplementarymaterial.docx Supplementary figures and tables SuppTable1.xlsx Supplemental table 1 Cite Share Download PDF Status: Posted Version 2 posted You are reading this latest preprint version Show more versions 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. 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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-4693768","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":329041169,"identity":"197e7d3a-8806-48cf-9f9b-2fc9a4962492","order_by":0,"name":"Anna 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