{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T12:15:40Z","timestamp":1776341740149,"version":"3.51.2"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioinform."],"abstract":"<jats:p>Viral adaptation across closely related hosts often proceeds through subtle molecular changes that escape detection by classical phylogenetic analyses. In waterfowl parvoviruses, we integrate AI-based protein language modeling, structural biophysics, and infection assays to reveal a continuous trajectory of host adaptation linking Goose parvovirus (GPV) and Muscovy duck parvovirus (MDPV). Protein embeddings of VP1 sequences reveal a smooth manifold bridging GPV and MDPV, which softens an apparent phylogenetic dichotomy into a graded molecular topology. Structural modeling identifies a flexible surface loop (residues 300\u2013420) as a biophysical pivot. Along the embedding trajectory, this loop undergoes gradual conformational expansion and electrostatic neutralization, quantitatively linking embedding coordinates to capsid surface remodeling. Experimentally, a GPV-type isolate recovered from naturally diseased ducks replicated efficiently in duck embryos, duck embryo fibroblasts, and live ducklings, producing characteristic lesions. These results show that waterfowl parvoviruses evolve along a continuous molecular\u2013electrostatic landscape in which cumulative structural adjustments enable cross-host infectivity. Our framework connects AI-derived molecular representations to biophysical mechanisms and biological function, supporting a model of viral host adaptation as a predominantly continuous process and providing a foundation for predicting cross-host potential in emerging viral systems.<\/jats:p>","DOI":"10.3389\/fbinf.2025.1738737","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T10:34:47Z","timestamp":1769510087000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Protein embeddings reveal a continuous molecular landscape of host adaptation in waterfowl parvoviruses"],"prefix":"10.3389","volume":"5","author":[{"given":"Nihui","family":"Shao","sequence":"first","affiliation":[{"name":"Faculty of Science, University of Bern","place":["Bern, Switzerland"]}]},{"given":"Yunfei","family":"Guo","sequence":"additional","affiliation":[{"name":"Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University","place":["Yangzhou, China"]}]}],"member":"1965","published-online":{"date-parts":[[2026,1,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e2397","DOI":"10.1371\/journal.pone.0002397","article-title":"Virus adaptation by manipulation of host\u2019s gene expression","volume":"3","author":"Agudelo-Romero","year":"2008","journal-title":"PLoS ONE"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1358","DOI":"10.3390\/v16091358","article-title":"AlphaFold2 reveals structural patterns of seasonal haplotype diversification in SARS-CoV-2 nucleocapsid protein variants","volume":"16","author":"Ali","year":"","journal-title":"Viruses"},{"key":"B3","doi-asserted-by":"publisher","first-page":"134","DOI":"10.3390\/biology13030134","article-title":"AlphaFold2 reveals structural patterns of seasonal haplotype diversification in SARS-CoV-2 spike protein variants","volume":"13","author":"Ali","year":"","journal-title":"Biology"},{"key":"B4","doi-asserted-by":"publisher","first-page":"176","DOI":"10.3389\/fcell.2018.00176","article-title":"A comprehensive review on the interaction between the host GTPase Rab11 and influenza a virus","volume":"6","author":"Amorim","year":"2019","journal-title":"Front. Cell Dev. Biol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1126\/science.abj8754","article-title":"Accurate prediction of protein structures and interactions using a three-track neural network","volume":"373","author":"Baek","year":"2021","journal-title":"Science"},{"key":"B6","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1186\/1471-2105-10-421","article-title":"BLAST+: architecture and applications","volume":"10","author":"Camacho","year":"2009","journal-title":"BMC Bioinforma."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1972","DOI":"10.1093\/bioinformatics\/btp348","article-title":"trimAl: a tool for automated alignment trimming in large-scale phylogenetic analyses","volume":"25","author":"Capella-Guti\u00e9rrez","year":"2009","journal-title":"Bioinformatics"},{"key":"B8","doi-asserted-by":"publisher","first-page":"e0140284","DOI":"10.1371\/journal.pone.0140284","article-title":"Isolation and genomic characterization of a duck-origin GPV-related parvovirus from cherry valley ducklings in China","volume":"10","author":"Chen","year":"2015","journal-title":"PLoS ONE"},{"key":"B9","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1109\/TIT.1967.1053964","article-title":"Nearest neighbor pattern classification","volume":"13","author":"Cover","year":"1967","journal-title":"IEEE Trans. Inf. Theory"},{"key":"B10","doi-asserted-by":"publisher","first-page":"W665","DOI":"10.1093\/nar\/gkh381","article-title":"PDB2PQR: an automated pipeline for the setup of poisson-boltzmann electrostatics calculations","volume":"32","author":"Dolinsky","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"7112","DOI":"10.1109\/TPAMI.2021.3095381","article-title":"ProtTrans: toward understanding the language of life through self-supervised learning","volume":"44","author":"Elnaggar","year":"2022","journal-title":"IEEE Trans. Pattern Anal. Mach. Intell."},{"key":"B12","doi-asserted-by":"publisher","first-page":"e00428-17","DOI":"10.1128\/genomeA.00428-17","article-title":"Complete genome sequence of a novel goose parvovirus isolated in Sichuan province, China, in 2016","volume":"5","author":"Ge","year":"2017","journal-title":"Genome Announc."},{"key":"B13","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1038\/s41576-018-0055-5","article-title":"The phylogenomics of evolving virus virulence","volume":"19","author":"Geoghegan","year":"2018","journal-title":"Nat. Rev. Genet."},{"key":"B14","doi-asserted-by":"publisher","first-page":"12211","DOI":"10.1128\/JVI.77.22.12211-12221.2003","article-title":"Structures of host range-controlling regions of the capsids of canine and feline parvoviruses and mutants","volume":"77","author":"Govindasamy","year":"2003","journal-title":"J. Virol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1016\/j.coviro.2013.07.001","article-title":"Viral host-adaptation: insights from evolution experiments with phages","volume":"3","author":"Hall","year":"2013","journal-title":"Curr. Opin. Virol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1126\/science.abd7331","article-title":"Learning the language of viral evolution and escape","volume":"371","author":"Hie","year":"2021","journal-title":"Science"},{"key":"B17","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1038\/nbt.3769","article-title":"Mutation effects predicted from sequence co-variation","volume":"35","author":"Hopf","year":"2017","journal-title":"Nat. Biotechnol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"B19","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1093\/molbev\/mst010","article-title":"MAFFT multiple sequence alignment software version 7: improvements in performance and usability","volume":"30","author":"Katoh","year":"2013","journal-title":"Mol. Biol. Evol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.3390\/pathogens11091039","article-title":"Determinants of virus variation, evolution, and host adaptation","volume":"11","author":"LaTourrette","year":"2022","journal-title":"Pathogens"},{"key":"B21","doi-asserted-by":"publisher","first-page":"3211","DOI":"10.3390\/ani11113211","article-title":"Molecular characterization and pathogenicity of the novel recombinant muscovy duck parvovirus isolated from geese","volume":"11","author":"Li","year":"2021","journal-title":"Animals"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e1004395","DOI":"10.1371\/journal.ppat.1004395","article-title":"The evolution and genetics of virus host shifts","volume":"10","author":"Longdon","year":"2014","journal-title":"PLoS Pathog."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1038\/s41587-022-01618-2","article-title":"Large language models generate functional protein sequences across diverse families","volume":"41","author":"Madani","year":"2023","journal-title":"Nat. Biotechnol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1038\/s41592-019-0456-1","article-title":"Pathway-level information extractor (PLIER) for gene expression data","volume":"16","author":"Mao","year":"2019","journal-title":"Nat. Methods"},{"key":"B25","doi-asserted-by":"publisher","first-page":"861","DOI":"10.21105\/joss.00861","article-title":"UMAP: uniform manifold approximation and projection","volume":"3","author":"McInnes","year":"2018","journal-title":"J. Open Source Softw."},{"key":"B26","doi-asserted-by":"publisher","first-page":"362","DOI":"10.3390\/v11040362","article-title":"Twenty-five years of structural parvovirology","volume":"11","author":"Mietzsch","year":"2019","journal-title":"Viruses"},{"key":"B27","doi-asserted-by":"publisher","first-page":"bbw068","DOI":"10.1093\/bib\/bbw068","article-title":"Deep learning in bioinformatics","volume":"18","author":"Min","year":"2016","journal-title":"Brief. Bioinform"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1530","DOI":"10.1093\/molbev\/msaa015","article-title":"IQ-TREE 2: new models and efficient methods for phylogenetic inference in the genomic era","volume":"37","author":"Minh","year":"2020","journal-title":"Mol. Biol. Evol."},{"key":"B29","volume-title":"Guide for the care and use of laboratory animals","year":"2011"},{"key":"B30","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.vetmic.2017.08.020","article-title":"Pathogenicity of Pekin duck- and goose-origin parvoviruses in Pekin ducklings","volume":"210","author":"Ning","year":"2017","journal-title":"Veterinary Microbiol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1080\/03079450902737839","article-title":"Short beak and dwarfism syndrome of mule duck is caused by a distinct lineage of goose parvovirus","volume":"38","author":"Palya","year":"2009","journal-title":"Avian Pathol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1128\/MMBR.00004-08","article-title":"Cross-species virus transmission and the emergence of new epidemic diseases","volume":"72","author":"Parrish","year":"2008","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"B33","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.tim.2019.08.007","article-title":"Species-specific host\u2013virus interactions: implications for viral host range and virulence","volume":"28","author":"Rothenburg","year":"2020","journal-title":"Trends Microbiol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/0377-0427(87)90125-7","article-title":"Silhouettes: a graphical aid to the interpretation and validation of cluster analysis","volume":"20","author":"Rousseeuw","year":"1987","journal-title":"J. Comput. Appl. Math."},{"key":"B35","doi-asserted-by":"publisher","first-page":"D141","DOI":"10.1093\/nar\/gkac1012","article-title":"GenBank 2023 update","volume":"51","author":"Sayers","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"B36","doi-asserted-by":"publisher","article-title":"The scikit-learn developers. Scikit-learn","year":"2024","DOI":"10.5281\/ZENODO.13749328"},{"key":"B37","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1038\/s41559-024-02353-4","article-title":"The evolutionary drivers and correlates of viral host jumps","volume":"8","author":"Tan","year":"2024","journal-title":"Nat. Ecol. Evol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1080\/03079450410001724067","article-title":"Phylogenetic analysis of Hungarian goose parvovirus isolates and vaccine strains","volume":"33","author":"Tat\u00e1r-kis","year":"2004","journal-title":"Avian Pathol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"267","DOI":"10.12688\/f1000research.131522.1","article-title":"Seasonal effects decouple SARS-CoV-2 haplotypes worldwide","volume":"12","author":"Tomaszewski","year":"2023","journal-title":"F1000Res"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1126\/science.abe5650","article-title":"Geometric deep learning of RNA structure","volume":"373","author":"Townshend","year":"2021","journal-title":"Science"},{"key":"B41","doi-asserted-by":"publisher","first-page":"D439","DOI":"10.1093\/nar\/gkab1061","article-title":"AlphaFold protein structure database: massively expanding the structural coverage of protein-sequence space with high-accuracy models","volume":"50","author":"Varadi","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"B42","doi-asserted-by":"publisher","first-page":"vez026","DOI":"10.1093\/ve\/vez026","article-title":"Changes on the viral capsid surface during the evolution of porcine circovirus type 2 (PCV2) from 2009 till 2018 may lead to a better receptor binding","volume":"5","author":"Wei","year":"2019","journal-title":"Virus Evol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1016\/j.tree.2005.02.009","article-title":"Emerging pathogens: the epidemiology and evolution of species jumps","volume":"20","author":"Woolhouse","year":"2005","journal-title":"Trends Ecol. Evol."},{"key":"B44","volume-title":"Laboratory biosafety manual. 4th ed","year":"2020"},{"key":"B45","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1016\/j.vetmic.2017.03.012","article-title":"The newly emerging duck-origin goose parvovirus in China exhibits a wide range of pathogenicity to main domesticated waterfowl","volume":"203","author":"Xiao","year":"2017","journal-title":"Veterinary Microbiol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1038\/s41579-021-00630-8","article-title":"Structural biology of SARS-CoV-2 and implications for therapeutic development","volume":"19","author":"Yang","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"e1298","DOI":"10.1002\/wcms.1298","article-title":"Using PyMOL as a platform for computational drug design","volume":"7","author":"Yuan","year":"2017","journal-title":"WIREs Comput. Mol. Sci."},{"key":"B48","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1006\/viro.1995.1514","article-title":"Analysis of the complete nucleotide sequences of goose and muscovy duck pervoviruses indicates common ancestral origin with adeno-associated virus 2","volume":"212","author":"Z\u00e1dori","year":"1995","journal-title":"Virology"}],"updated-by":[{"DOI":"10.3389\/fbinf.2026.1839097","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000}}],"container-title":["Frontiers in Bioinformatics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbinf.2025.1738737\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T11:34:42Z","timestamp":1776339282000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbinf.2025.1738737\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,27]]},"references-count":48,"alternative-id":["10.3389\/fbinf.2025.1738737"],"URL":"https:\/\/doi.org\/10.3389\/fbinf.2025.1738737","relation":{},"ISSN":["2673-7647"],"issn-type":[{"value":"2673-7647","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,27]]},"article-number":"1738737"}}