Conserved recombination patterns across hepatitis B genotypes: a retrospective study

Conserved recombination patterns across hepatitis B genotypes: a retrospective study | 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 Research Article Conserved recombination patterns across hepatitis B genotypes: a retrospective study Derek Tshiabuila, James E. San, Eduan Wilkinson, Graeme Dor, Houriiyah Tegally, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6471700/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 05 Jul, 2025 Read the published version in Virology Journal → Version 1 posted 7 You are reading this latest preprint version Abstract Hepatitis B virus (HBV) infection is a major public health concern, as chronic HBV infection can lead to liver cirrhosis and increase a person’s risk of developing hepatocellular carcinoma (HCC). HBV has been classified into ten genotypes (A to J). Here, we analysed the genotypic diversity and recombination patterns of HBV using 14486 publicly available HBV genome sequences. Partial sequences and sequences with no metadata were filtered out, resulting in a final dataset of 8823 HBV genomes. These sequences were then combined with 41 HBV reference genomes from NCBI GenBank, and a maximum-likelihood phylogenetic tree was constructed to generate ten HBV genotype datasets. Multiple sequence alignment was performed for each HBV dataset, and using RDP5.64, we identified 288 unique recombination events. Inter-genotype B/C recombination events were most common (found in 626/1194 identified recombinants), including 22/66 recombination events detected in viruses that are phylogenetically genotype B and 22/78 that are phylogenetically genotype C. The HBx (X) and pre-Core (pre-C) regions of the HBV genome were identified as recombination breakpoint hotspots, with the pre-C region also being the most frequently transferred genome region during recombination. As with many other viruses, the observed recombination breakpoint patterns in HBV genomes are significantly attributable to factors such as local sequence similarity, GC content, or selection against recombination-induced protein misfolding. This study highlights the complexity of the genetic diversity and recombination of HBV, with important implications for understanding its evolution and informing tailored public health interventions. Hepatitis B virus (HBV) Genotypic diversity Viral recombination Recombination hotspots Phylogenetics Viral evolution Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 05 Jul, 2025 Read the published version in Virology Journal → Version 1 posted Editorial decision: Revision requested 30 May, 2025 Reviews received at journal 28 May, 2025 Reviewers agreed at journal 22 May, 2025 Reviewers invited by journal 05 May, 2025 Editor assigned by journal 25 Apr, 2025 Submission checks completed at journal 25 Apr, 2025 First submitted to journal 17 Apr, 2025 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. 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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-6471700","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":453290890,"identity":"e44d8cca-eb58-45c5-956e-b04c9b0141be","order_by":0,"name":"Derek Tshiabuila","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDUlEQVRIie3NsUrDUBTG8S8EbpeYrjcgzSucUBCHYl/lhkK6JEFwESwxU1wqrnHqK+QRIoFkiXucTBanIrjFQTAVXKQX6+Zw/8OZzo8PUKn+YzmgxYBgMIZ7jsmBRHwTwvRwgh0BwY1/E2Z123X3fRSao8eSt3S23KRBjn6F+ViCrbqaOpkoLpgRelzQIsiaUGjrEjrP9xNqPGa1IncT+CcD0YOM+4SjGAwy8vwyem9F5Cbj7Y5cL+3UJ+0jhmFLVxjTMqG7Cf9aKQQan/RhhZOEWLWnW6lXDOR1cSqocrJ6S8VxycmRELMqtbf1LHI3d8HDU395Zds3vtNtV7P5REL2Nzzzv/yrVCqV6kefzkNbAq9vgk4AAAAASUVORK5CYII=","orcid":"","institution":"Stellenbosch University","correspondingAuthor":true,"prefix":"","firstName":"Derek","middleName":"","lastName":"Tshiabuila","suffix":""},{"id":453290891,"identity":"9fa94f6c-4495-4ce5-9381-8a7abad45269","order_by":1,"name":"James E. 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