Extrinsic Ecological Factors and Intrinsic Genetic Features are Associated with Ecological Generalism in Pathogenic Tick-Borne Viruses

Extrinsic Ecological Factors and Intrinsic Genetic Features are Associated with Ecological Generalism in Pathogenic Tick-Borne Viruses | 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 Analysis Extrinsic Ecological Factors and Intrinsic Genetic Features are Associated with Ecological Generalism in Pathogenic Tick-Borne Viruses Xuebing Ni, Yong-Tao Ye, Gong-Pei Wang, Ye-Xiao Cheng, Yuqian Wu, and 13 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7258590/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 Emerging and re-emerging tick-borne viruses (TBVs) have caused numerous outbreaks recently, yet the factors driving their emergence and pathogenicity in humans remain unclear. A global analysis integrating epidemiological and genomic data of all known pathogenic TBVs revealed that highly pathogenic TBVs (HPTBVs) tend to exhibit ecological generalism. Specifically, HPTBVs infect a broader range of tick species, animal hosts, and ecotypes, which likely enhance their transmission to humans. Bird migration is the primary driver for geographic spread of HPTBVs, while livestock density and TBVs’ diversity they carry determine HPTBVs local persistence. HPTBVs experience stronger positive selection in genes related to host interactions, with specific mutations associated with lineage adaptation. Notably, the positively selected D170N mutation in severe fever with thrombocytopenia syndrome virus revealed an enhanced binding affinity to human receptors, which correlated with increased infectivity. These findings underscore ecological and evolutionary factors facilitating TBV generalization, thereby posing significant public health risks. Biological sciences/Evolution/Molecular evolution Biological sciences/Ecology/Ecological modelling Earth and environmental sciences/Ecology/Evolutionary ecology Biological sciences/Zoology Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Full Text Additional Declarations There is NO Competing Interest. Supplementary Files FigS120250503.pdf Extended Data Figure 1 FigS2plotwholehostFlaviviridae20250206.pdf Extended Data Figure 2 FigS3plotwholehostNairoviridae20250206.pdf Extended Data Figure 3 FigS4plotwholehostPhenuiviridae20250206.pdf Extended Data Figure 4 FigS5plotwholehostOther20250206.pdf Extended Data Figure 5 FigS620250503.pdf Extended Data Figure 6 FigS720250503.pdf Extended Data Figure 7 FigS8Barplotthreemodelmeanvalue.pdf Extended Data Figure 8 Supplementarytable.pdf Supplementary table 1-5 Metareviewreference.pdf Meta-review reference 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. 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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-7258590","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Analysis","associatedPublications":[],"authors":[{"id":500610940,"identity":"f2e93676-2605-4842-ad7b-4fca10a1f435","order_by":0,"name":"Xuebing Ni","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3klEQVRIiWNgGAWjYDACZiBmbJBgYJB/fPBBQkUNKVoY0pINHpw5RqRNjA0gMsdM8mELM2HV5uw8ZhIfd1jkyTscMKtIbGBj4G/vTsCrxbKZLU1y5hmJYsODDWk3EnfIMEicObsBrxaDw8zHpHnbJBI3NjMcu5F4ho3BQCKXkBbGNum/IC1tjG0FiW3MxGgB2sII1DKfh5mNgUgtbMmWvWckEjdIsDFLJJw5xkPYL+fPGN74uaMucf4M/o8ff1TUyPG39+LXgtB7AELzEKccBOQbiFc7CkbBKBgFIwwAAGeiSLosBeEhAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-5542-8165","institution":"The University of Hong Kong","correspondingAuthor":true,"prefix":"","firstName":"Xuebing","middleName":"","lastName":"Ni","suffix":""},{"id":500610941,"identity":"2488c25f-e10b-41f8-aeec-f36903dbc9b7","order_by":1,"name":"Yong-Tao Ye","email":"","orcid":"","institution":"State Key Laboratory of Emerging Infectious Diseases and Centre of Influenza Research, School of Public Health, The University of Hong Kong, Hong Kong SAR, P. 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The virus icons on the map indicate the locations of the first discoveries of virus records; c, The timeline of the first discoveries and the first human case records for PTBVs.\u003c/p\u003e","description":"","filename":"Fig120250430v5.png","url":"https://assets-eu.researchsquare.com/files/rs-7258590/v1/6574a75dedc7eb02eebd7396.png"},{"id":90068143,"identity":"44feb2b5-ddce-4809-9e4e-6eacd456c23d","added_by":"auto","created_at":"2025-08-28 06:08:17","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":217809,"visible":true,"origin":"","legend":"\u003cp\u003eHost range and preference of pathogenic tick-borne viruses. a, Illustration of viral genome characteristics, ecotype distributions, and transmission mode of PTBVs; b, The prevalence, case numbers, and ecological generalism index of PTBVs in humans according to the meta-review analysis; c, The prevalence and richness of PTBVs in each tick genus; d, The prevalence and richness of PTBVs in each animal order or class.\u003c/p\u003e","description":"","filename":"Fig220250430v4.png","url":"https://assets-eu.researchsquare.com/files/rs-7258590/v1/5af72051a855923e8ef47736.png"},{"id":90068145,"identity":"43e8c1d1-a335-423e-99a9-9989f88a39fd","added_by":"auto","created_at":"2025-08-28 06:08:18","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":99517,"visible":true,"origin":"","legend":"\u003cp\u003eEcological drivers for the long-distance dissemination of HPTBVs. a-d, Correlation between predictors and viral geographic transition frequency from GLM analyses in BEAST. Posterior summaries of the product (log effect size) of the log constant through- time predictor coefficient and the predictor inclusion probability (pooled across time periods) for TBEV, CCHFV and JMTV lineages were presented. Points indicated the posterior mean, while ranges represent the 95% highest posterior density (HPD) intervals. Location-specific predictors were included as both origin (O) and destination.\u003c/p\u003e","description":"","filename":"Fig320250617v1.png","url":"https://assets-eu.researchsquare.com/files/rs-7258590/v1/f0cf6144c036a2b9f89c5f20.png"},{"id":90068157,"identity":"f48eb539-8a88-4956-8fe3-3bcd5452fa08","added_by":"auto","created_at":"2025-08-28 06:08:20","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":224903,"visible":true,"origin":"","legend":"\u003cp\u003eEcological drivers for the occurrence and diversity of pathogenic tick-borne viruses. a, Model performance for the best model of Boosted Regression Trees (BRT), Random Forest (RF), and Support Vector Machine (SVM). b-e, Importance of eco-climate factors for the occurrence of PTBVs and HPTBVs from the best BRT model; f, Partial effect of PTBVs diversity in animals for human PTBVs richness by General Additive Model (GAM); g, Partial effect of PTBVs diversity in ticks for human PTBVs richness by GAM; h, Interaction effect between PTBVs diversity in animals and ticks for human PTBVs richness by GAM.\u003c/p\u003e","description":"","filename":"Fig420250430v6.png","url":"https://assets-eu.researchsquare.com/files/rs-7258590/v1/acd03789fc976781723d6c88.png"},{"id":90068136,"identity":"dd080db4-02de-4544-b3b9-048aab3e48a1","added_by":"auto","created_at":"2025-08-28 06:08:17","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":116008,"visible":true,"origin":"","legend":"\u003cp\u003eMolecular adaptation favors the pathogenicity of HPTBVs. a, The ratio of nonsynonymous and synonymous substitutions per site (dN/dS) on internal branches in cell- interaction genes and replicase genes among HPTBVs, LPTBVs, and NPTBVs at the species level; b-e, Phylogenetic trees and positively selected amino acid mutation of CCHFV glycoprotein, SFTSV glycoprotein, JMTV glycoprotein and membrane protein.\u003c/p\u003e","description":"","filename":"Fig520250617v1.png","url":"https://assets-eu.researchsquare.com/files/rs-7258590/v1/1cf6b926ca5a42a1d06cd543.png"},{"id":90068111,"identity":"45de116d-3892-43c1-b453-e499798f250c","added_by":"auto","created_at":"2025-08-28 06:08:14","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":757197,"visible":true,"origin":"","legend":"\u003cp\u003eComparative structural analysis of the SFTSV glycoprotein-N D170N substitution and human prolow-density lipoprotein receptor-related protein 1 (LRP1) a, Proportion of 170N variants and case fatality rate among different SFTSV genotypes from meta-review analysis; b, Geographic distribution of 170N variants and regional incidence of SFTSV from meta-review analysis; c, Structural overview of SFTSV glycoprotein N (Gn, blue) and glycoprotein C (Gc, brown) bound to human LRP1 (pink), as derived by ZDOCK; d, Zoom of the 170D in relation to proximal amino acid side chains; e, Derived 170N variant in relation to proximal amino acid 172A of LRP1.\u003c/p\u003e","description":"","filename":"Fig620250729v1.png","url":"https://assets-eu.researchsquare.com/files/rs-7258590/v1/ce2159fb73545f5095fff339.png"},{"id":90069084,"identity":"a514b617-968b-41c3-8b4e-5d253ae21296","added_by":"auto","created_at":"2025-08-28 06:24:20","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1820737,"visible":true,"origin":"","legend":"Article File","description":"","filename":"TBVmanuscriptv17xb.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7258590/v1_covered_5d174326-b294-40fd-af9f-f347e6e2ea20.pdf"},{"id":90068146,"identity":"f65f9014-224b-4945-9660-04b59b9d1f08","added_by":"auto","created_at":"2025-08-28 06:08:18","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":614957,"visible":true,"origin":"","legend":"Extended Data Figure 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Viruses","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature 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A global analysis integrating epidemiological and genomic data of all known pathogenic TBVs revealed that highly pathogenic TBVs (HPTBVs) tend to exhibit ecological generalism. Specifically, HPTBVs infect a broader range of tick species, animal hosts, and ecotypes, which likely enhance their transmission to humans. Bird migration is the primary driver for geographic spread of HPTBVs, while livestock density and TBVs’ diversity they carry determine HPTBVs local persistence. HPTBVs experience stronger positive selection in genes related to host interactions, with specific mutations associated with lineage adaptation. Notably, the positively selected D170N mutation in severe fever with thrombocytopenia syndrome virus revealed an enhanced binding affinity to human receptors, which correlated with increased infectivity. These findings underscore ecological and evolutionary factors facilitating TBV generalization, thereby posing significant public health risks.","manuscriptTitle":"Extrinsic Ecological Factors and Intrinsic Genetic Features are Associated with Ecological Generalism in Pathogenic Tick-Borne Viruses","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-28 06:08:08","doi":"10.21203/rs.3.rs-7258590/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"nature-communications","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"NCOMMS","sideBox":"Learn more about [Nature Communications](http://www.nature.com/ncomms/)","snPcode":"","submissionUrl":"https://mts-ncomms.nature.com/","title":"Nature Communications","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Communications","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"4071da2c-d71e-4887-921e-10c9ffd5bae8","owner":[],"postedDate":"August 28th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":53183849,"name":"Biological sciences/Evolution/Molecular evolution"},{"id":53183850,"name":"Biological sciences/Ecology/Ecological modelling"},{"id":53183851,"name":"Earth and environmental sciences/Ecology/Evolutionary ecology"},{"id":53183852,"name":"Biological sciences/Zoology"}],"tags":[],"updatedAt":"2025-08-28T06:08:08+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-28 06:08:08","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7258590","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7258590","identity":"rs-7258590","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}