{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:31:16Z","timestamp":1772253076143,"version":"3.50.1"},"reference-count":34,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T00:00:00Z","timestamp":1753228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Background: Parvovirus B19 (B19V) can cause severe relapsing episodes of pure red cell aplasia in immunocompromised individuals, which are commonly treated with intravenous immunoglobulins (IVIGs). Few data are available on B19V intra-host evolution and the role of humoral immune selection. Here, we report the dynamics of genomic mutations and subsequent protein changes during relapsing infection. Methods: Longitudinal plasma samples from immunocompromised patients with relapsing B19V infection in the period 2011\u20132019 were analyzed using whole-genome sequencing to evaluate intra-host evolution. The impact of mutations on the 3D viral protein structure was predicted by deep neural network modeling. Results: Of the three immunocompromised patients with relapsing infections for 3 to 9 months, one patient developed two consecutive nonsynonymous mutations in the VP1\/2 region: T372S\/T145S and Q422L\/Q195L. The first mutation was detected in multiple B19V IgG-seropositive follow-up samples and resolved after IgG seroreversion. Computational prediction of the VP1 3D structure of this mutant showed a conformational change in the proximity of the antibody binding domain. No conformational changes were predicted for the other mutations detected. Discussion: Analysis of relapsing B19V infections showed mutational changes occurring over time. Resulting amino acid changes were predicted to lead to a conformational capsid protein change in an IgG-seropositive patient. The impact of humoral response and IVIG treatment on B19V infections should be further investigated to understand viral evolution and potential immune escape.<\/jats:p>","DOI":"10.3390\/v17081034","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T14:22:44Z","timestamp":1753280564000},"page":"1034","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Intra-Host Evolution During Relapsing Parvovirus B19 Infection in Immunocompromised Patients"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-2186-5410","authenticated-orcid":false,"given":"Anne","family":"Russcher","sequence":"first","affiliation":[{"name":"Medical Microbiology and Infection Control, Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center (LUMC), 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3265-3332","authenticated-orcid":false,"given":"Yassene","family":"Mohammed","sequence":"additional","affiliation":[{"name":"Center for Proteomics and Metabolomics, Leiden University Medical Center (LUMC), 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1723-4570","authenticated-orcid":false,"given":"Margriet E. M.","family":"Kraakman","sequence":"additional","affiliation":[{"name":"Medical Microbiology and Infection Control, Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center (LUMC), 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2948-8445","authenticated-orcid":false,"given":"Xavier","family":"Chow","sequence":"additional","affiliation":[{"name":"Center for Proteomics and Metabolomics, Leiden University Medical Center (LUMC), 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stijn T.","family":"Kok","sequence":"additional","affiliation":[{"name":"Center for Proteomics and Metabolomics, Leiden University Medical Center (LUMC), 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric C. J.","family":"Claas","sequence":"additional","affiliation":[{"name":"Medical Microbiology and Infection Control, Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center (LUMC), 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0814-4995","authenticated-orcid":false,"given":"Manfred","family":"Wuhrer","sequence":"additional","affiliation":[{"name":"Center for Proteomics and Metabolomics, Leiden University Medical Center (LUMC), 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1750-2843","authenticated-orcid":false,"given":"Ann C. T. M.","family":"Vossen","sequence":"additional","affiliation":[{"name":"Medical Microbiology and Infection Control, Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center (LUMC), 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aloys C. M.","family":"Kroes","sequence":"additional","affiliation":[{"name":"Medical Microbiology and Infection Control, Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center (LUMC), 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2530-6260","authenticated-orcid":false,"given":"Jutte J. C.","family":"de Vries","sequence":"additional","affiliation":[{"name":"Medical Microbiology and Infection Control, Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center (LUMC), 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ganaie, S.S., and Qiu, J. (2018). Recent Advances in Replication and Infection of Human Parvovirus B19. Front. Cell Infect. Microbiol., 8.","DOI":"10.3389\/fcimb.2018.00166"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e13535","DOI":"10.1111\/ctr.13535","article-title":"Human parvovirus B19 in solid organ transplantation: Guidelines from the American society of transplantation infectious diseases community of practice","volume":"33","author":"Eid","year":"2019","journal-title":"Clin. Transplant."},{"key":"ref_3","first-page":"265","article-title":"Treatment strategies and outcome of parvovirus B19 infection in kidney transplant recipients: A case series and literature review of 128 patients","volume":"71","year":"2019","journal-title":"Rev. Investig. Clin."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1038\/s41591-021-01472-w","article-title":"The next phase of SARS-CoV-2 surveillance: Real-time molecular epidemiology","volume":"27","author":"Worp","year":"2021","journal-title":"Nat. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1086\/598684","article-title":"Prolonged influenza virus infection during lymphocytopenia and frequent detection of drug-resistant viruses","volume":"199","author":"Gooskens","year":"2009","journal-title":"J. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1002\/rmv.1873","article-title":"Human cytomegalovirus antiviral drug resistance in hematopoietic stem cell transplantation: Current state of the art","volume":"26","author":"Campos","year":"2016","journal-title":"Rev. Med. Virol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.3201\/eid2809.220875","article-title":"Highly Divergent SARS-CoV-2 Alpha Variant in Chronically Infected Immunocompromised Person","volume":"28","author":"Nijhuis","year":"2022","journal-title":"Emerg. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1007\/BF01315420","article-title":"Extent of sequence variability in a genomic region coding for capsid proteins of B19 parvovirus","volume":"40","author":"Gallinella","year":"1995","journal-title":"Arch. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1002\/jmv.20708","article-title":"Genetic drift of parvovirus B19 is found in AIDS patients with persistent B19 infection","volume":"78","author":"Hung","year":"2006","journal-title":"J. Med. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e65","DOI":"10.1097\/MPH.0000000000000008","article-title":"Long-term parvovirus B19 infections with genetic drift after cord blood transplantation complicated by persistent CD4+ lymphocytopenia","volume":"36","author":"Suzuki","year":"2014","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.jcv.2004.05.015","article-title":"Long-term parvovirus B19 viraemia associated with pure red cell aplasia after allogeneic bone marrow transplantation","volume":"31","author":"Plentz","year":"2004","journal-title":"J. Clin. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"197963","DOI":"10.1016\/j.virusres.2020.197963","article-title":"Applying next-generation sequencing to unravel the mutational landscape in viral quasispecies","volume":"283","author":"Lu","year":"2020","journal-title":"Virus Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.jviromet.2019.01.013","article-title":"Application of deep sequencing methods for inferring viral population diversity","volume":"266","author":"Huang","year":"2019","journal-title":"J. Virol. Methods."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.jcv.2012.04.023","article-title":"Human parvovirus B19 genotype 3 associated with chronic anemia after stem cell transplantation, missed by routine PCR testing","volume":"54","author":"Knoester","year":"2012","journal-title":"J. Clin. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Carbo, E.C., Russcher, A., Kraakman, M.E.M., de Brouwer, C.S., Sidorov, I.A., Feltkamp, M.C.W., Kroes, A.C.M., Claas, E.C., and de Vries, J.J.C. (2022). Longitudinal Monitoring of DNA Viral Loads in Transplant Patients Using Quantitative Metagenomic Next-Generation Sequencing. Pathogens, 11.","DOI":"10.3390\/pathogens11020236"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1038\/s41586-021-03828-1","article-title":"Highly accurate protein structure prediction for the human proteome","volume":"596","author":"Tunyasuvunakool","year":"2021","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"w431","DOI":"10.1093\/nar\/gkab314","article-title":"Mol* Viewer: Modern web app for 3D visualization and analysis of large biomolecular structures","volume":"49","author":"Sehnal","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Guo, H.B., Huntington, B., Perminov, A., Smith, K., Hastings, N., Dennis, P., Kelley-Loughnane, N., and Berry, R. (2024). AlphaFold2 modeling and molecular dynamics simulations of an intrinsically disordered protein. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0301866"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"11628","DOI":"10.1073\/pnas.0402992101","article-title":"The structure of human parvovirus B19","volume":"101","author":"Kaufmann","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e01732-18","DOI":"10.1128\/JVI.01732-18","article-title":"Structure of Parvovirus B19 decorated by Fabs from a human antibody","volume":"93","author":"Sun","year":"2019","journal-title":"J. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3004","DOI":"10.1128\/jvi.67.6.3004-3009.1993","article-title":"Neutralizing linear epitopes of B19 parvovirus cluster in the VP1 unique and VP1-VP2 junction regions","volume":"67","author":"Saikawa","year":"1993","journal-title":"J. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/S0042-6822(95)80079-4","article-title":"Peptides derived from the unique region of B19 parvovirus minor capsid protein elicit neutralizing antibodies in rabbits","volume":"206","author":"Anderson","year":"1995","journal-title":"Virology"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Ros, C., Bieri, J., and Leisi, R. (2020). The VP1u of Human Parvovirus B19: A Multifunctional Capsid Protein with Biotechnological Applications. Viruses, 12.","DOI":"10.3390\/v12121463"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"7056","DOI":"10.1128\/jvi.65.12.7056-7060.1991","article-title":"A second neutralizing epitope of B19 parvovirus implicates the spike region in the immune response","volume":"65","author":"Yoshimoto","year":"1991","journal-title":"J. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.meegid.2017.11.021","article-title":"Incidence and progression of Parvovirus B19 infection and molecular changes in circulating B19V strains in children with haematological malignancy: A follow up study","volume":"57","author":"Jain","year":"2018","journal-title":"Infect. Genet. Evol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3666","DOI":"10.1128\/JVI.80.7.3666-3669.2006","article-title":"Phylogenetic evidence for the rapid evolution of human B19 erythrovirus","volume":"80","author":"Shackelton","year":"2006","journal-title":"J. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"7450","DOI":"10.1073\/pnas.0602259103","article-title":"Bioportfolio: Lifelong persistence of variant and prototypic erythrovirus DNA genomes in human tissue","volume":"103","author":"Norja","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"10975","DOI":"10.1128\/JVI.00273-09","article-title":"Analysis of nucleotide sequences of human parvovirus B19 genome reveals two different modes of evolution, a gradual alteration and a sudden replacement: A retrospective study in Sapporo, Japan, from 1980 to 2008","volume":"83","author":"Suzuki","year":"2009","journal-title":"J. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Toppinen, M., Perdomo, M.F., Palo, J.U., Simmonds, P., Lycett, S.J., Soderlund-Venermo, M., Sajantila, A., and Hedman, K. (2015). Bones hold the key to DNA virus history and epidemiology. Sci. Rep., 5.","DOI":"10.1038\/srep17226"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Stamenkovi\u0107, G.G., \u0106irkovi\u0107, V.S., \u0160ilji\u0107, M.M., Blagojevi\u0107, J.V., Kne\u017eevi\u0107, A.M., Joksi\u0107, I.D., and Stanojevi\u0107, M.P. (2016). Substitution rate and natural selection in parvovirus B19. Sci. Rep., 6.","DOI":"10.1038\/srep35759"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7557","DOI":"10.1073\/pnas.1804921115","article-title":"Ancient human parvovirus B19 in Eurasia reveals its long-term association with humans","volume":"115","author":"Margaryan","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e68612","DOI":"10.7554\/eLife.68612","article-title":"Ancient viral genomes reveal introduction of human pathogenic viruses into Mexico during the transatlantic slave trade","volume":"10","author":"Wesp","year":"2021","journal-title":"Elife"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/nrg2323","article-title":"Rates of evolutionary change in viruses: Patterns and determinants","volume":"9","author":"Duffy","year":"2008","journal-title":"Nat. Rev. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/nrg.2015.8","article-title":"Bayesian molecular clock dating of species divergences in the genomics era","volume":"17","author":"Donoghue","year":"2016","journal-title":"Nat. Rev. Genet."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/8\/1034\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:14:51Z","timestamp":1760033691000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/8\/1034"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,23]]},"references-count":34,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["v17081034"],"URL":"https:\/\/doi.org\/10.3390\/v17081034","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.10.04.24314882","asserted-by":"object"}]},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,23]]}}}