A pan-orthohantavirus preclinical human lung xenograft mouse model

A pan-orthohantavirus preclinical human lung xenograft mouse model | 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 A pan-orthohantavirus preclinical human lung xenograft mouse model Melanie Rissmann, Danny Noack, Thomas Spliethof, Vincent Vaes, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3999668/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Orthohantaviruses are emerging zoonotic viruses that can infect humans via the respiratory tract. There is a clear unmet need for an in vivo model to study orthohantavirus infection in physiologically relevant tissue and to determine the broad reactivity of novel orthohantavirus countermeasures. Here, we describe the use of a human lung xenograft mouse model to study the permissiveness for different orthohantavirus species and to assess its utility for preclinical testing of pan-orthohantavirus therapeutics. Following infection of xenografted human lung tissues, distinct orthohantavirus species differentially replicated in the human lung and subsequently spread systemically. The different orthohantaviruses primarily targeted the endothelium, respiratory epithelium and macrophages. Treatment of these mice with a virus neutralizing antibody could block orthohantavirus infection and dissemination. This model will facilitate progress in the fundamental understanding of pathogenesis and virus-host interactions for orthohantaviruses. Furthermore, it is an invaluable tool for preclinical evaluation of novel candidate pan-orthohantavirus intervention strategies. Biological sciences/Microbiology/Virology/Viral pathogenesis Biological sciences/Microbiology/Virology/Antivirals Biological sciences/Microbiology/Virology/Virus–host interactions orthohantavirus hantavirus xenograft preclinical model antibody pan orthohantavirus Full Text Additional Declarations Yes there is potential Competing Interest. The Icahn School of Medicine at Mount Sinai has filed patent applications relating to SARS-CoV-2 serological assays, NDV-based SARS-CoV-2 vaccines, influenza virus vaccines and influenza virus therapeutics which list Florian Krammer as co-inventor and of which several have been licensed. Mount Sinai has spun out a company, Kantaro, to market serological tests for SARS-CoV-2 and another company, Castlevax, to develop SARS-CoV-2 vaccines. Florian Krammer is co-founder and scientific advisory board member of Castlevax. Florian Krammer has consulted for Merck, Curevac, Seqirus and Pfizer and is currently consulting for 3rd Rock Ventures, GSK, Gritstone and Avimex. The Krammer laboratory is also collaborating with Dynavax on influenza vaccine development. All other authors have no conflicts of interest to report. Supplementary Files Supplementaryinformationcompressed.pdf Cite Share Download PDF Status: Posted 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-3999668","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":276573691,"identity":"7e0e9009-55e1-4b02-b3dd-032e2766809e","order_by":0,"name":"Melanie 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