Human Coronavirus Infection Reorganizes Spatial Genomic Architecture in Permissive Lung Cells.

Human Coronavirus Infection Reorganizes Spatial Genomic Architecture in Permissive Lung Cells. | 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 Human Coronavirus Infection Reorganizes Spatial Genomic Architecture in Permissive Lung Cells. Karissa Sanbonmatsu, Ankush Singhal, Cullen Roth, Sofiya N. Micheva-Viteva, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3979539/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 Chromatin conformation capture followed by next-generation sequencing in combination with large-scale polymer simulations (4DHiC) produces detailed information on genomic loci interactions, allowing for the interrogation of 3D spatial genomic structures. Here, Hi-C data was acquired from the infection of fetal lung fibroblast (MRC5) cells with α-coronavirus 229E (CoV229E). Experimental Hi-C contact maps were used to determine viral-induced changes in genomic architecture over a 48-hour time period following viral infection, revealing substantial alterations in contacts within chromosomes and in contacts between different chromosomes. To gain further structural insight and quantify the underlying changes, we applied the 4DHiC polymer simulation method to reconstruct the 3D genomic structures and dynamics corresponding to the Hi-C maps. The models successfully reproduced experimental Hi-C data, including the changes in contacts induced by viral infection. Our 3D spatial simulations uncovered widespread chromatin restructuring, including increased chromosome compactness and A-B compartment mixing arising from infection. Our model also suggests increased spatial accessibility to regions containing interferon-stimulated genes upon infection with CoV229E, followed by chromatin restructuring at later time points, potentially inducing the migration of chromatin into more compact regions. This is consistent with previously observed suppression of gene expression. Our spatial genomics study provides a mechanistic structural basis for changes in chromosome architecture induced by coronavirus infection in lung cells. Biological sciences/Biophysics/Computational biophysics Biological sciences/Computational biology and bioinformatics/Genome informatics Biological sciences/Genetics/Genomics Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SI.pdf SI 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-3979539","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":278765065,"identity":"942c231a-870e-4942-a10c-43234efea768","order_by":0,"name":"Karissa Sanbonmatsu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAp0lEQVRIiWNgGAWjYBACCQYGxgcPGBhkSNLCbJDAwMBDkhY2CdK0SM5If1aRUHOHh4F/8TEJorRIS+SY3Ug49oyHQeJZGnFa5CRy2G4ksB0GajljbECklvRnBQn/SNEiLZFgxpDYBtTC32P4gCgtkj1vjCUS+w7zsEmwJRKnReJ4+sMPH74dluPnP3zgAFFaGAQSIDQ4dogD/AfQGaNgFIyCUTAK0AAATVorss4ldM4AAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-7965-7392","institution":"Los Alamos National Laboratory","correspondingAuthor":true,"prefix":"","firstName":"Karissa","middleName":"","lastName":"Sanbonmatsu","suffix":""},{"id":278765066,"identity":"849860fe-6217-46c2-bee8-7654c7aadbb9","order_by":1,"name":"Ankush Singhal","email":"","orcid":"","institution":"Los Alamos National Laboratory","correspondingAuthor":false,"prefix":"","firstName":"Ankush","middleName":"","lastName":"Singhal","suffix":""},{"id":278765067,"identity":"9f3b76ba-f8f6-4354-b953-fe75c3a7c063","order_by":2,"name":"Cullen Roth","email":"","orcid":"https://orcid.org/0000-0003-4934-6160","institution":"Los Alamos National Lab","correspondingAuthor":false,"prefix":"","firstName":"Cullen","middleName":"","lastName":"Roth","suffix":""},{"id":278765068,"identity":"1dd8bc44-4363-434b-991e-368e53bef134","order_by":3,"name":"Sofiya N. 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Here, Hi-C data was acquired from the infection of fetal lung fibroblast (MRC5) cells with α-coronavirus 229E (CoV229E). Experimental Hi-C contact maps were used to determine viral-induced changes in genomic architecture over a 48-hour time period following viral infection, revealing substantial alterations in contacts within chromosomes and in contacts between different chromosomes. To gain further structural insight and quantify the underlying changes, we applied the 4DHiC polymer simulation method to reconstruct the 3D genomic structures and dynamics corresponding to the Hi-C maps. The models successfully reproduced experimental Hi-C data, including the changes in contacts induced by viral infection. Our 3D spatial simulations uncovered widespread chromatin restructuring, including increased chromosome compactness and A-B compartment mixing arising from infection. Our model also suggests increased spatial accessibility to regions containing interferon-stimulated genes upon infection with CoV229E, followed by chromatin restructuring at later time points, potentially inducing the migration of chromatin into more compact regions. This is consistent with previously observed suppression of gene expression. 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