{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T00:13:46Z","timestamp":1793060026600,"version":"4.5.0"},"reference-count":49,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T00:00:00Z","timestamp":1673568000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003107","name":"Bundesministerium f\u00fcr Gesundheit","doi-asserted-by":"publisher","award":["ZMVI1\u20102518FSB705"],"award-info":[{"award-number":["ZMVI1\u20102518FSB705"]}],"id":[{"id":"10.13039\/501100003107","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007570","name":"Claussen-Simon-Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007570","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["10169096"],"award-info":[{"award-number":["10169096"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>Hepatitis E virus is a major cause of acute hepatitis worldwide and can progress to chronicity in immunocompromised individuals. Various virus\u2013host recombination events have been reported in the hypervariable region of the hepatitis E virus genome, but the patterns of assembly and selection remain unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To gain further insight into viral evolution, we assessed the presence of low abundance variants in 16 samples from individuals with acute or chronic infection using a targeted next\u2010generation sequencing approach.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In seven samples, different variants with insertions and\/or deletions were identified. Among them, eight insertions originating either from human genes or from the hepatitis E virus genome. Five different deletions could be identified. The amino acid composition of sequences with insertions showed a higher frequency of lysine and a lower abundance of proline, and additionally acetylation and ubiquitination sites were more frequent than in hepatitis E virus wild\u2010type sequences.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings suggest that the nucleotide composition of insertions and sites for post\u2010translational modification may contribute to recombination events. Although the impact of low\u2010level hepatitis E virus variants is uncertain, our results highlight the importance of a highly sensitive next\u2010generation sequencing approach to capture the full diversity of hypervariable region.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.15517","type":"journal-article","created":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T05:01:15Z","timestamp":1673240475000},"page":"794-804","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Insertions and deletions in the hypervariable region of the hepatitis E virus genome in individuals with acute and chronic infection"],"prefix":"10.1111","volume":"43","author":[{"given":"Paula","family":"Biedermann","sequence":"first","affiliation":[{"name":"Division of Viral Gastroenteritis and Hepatitis Pathogens and Enteroviruses, Department of Infectious Diseases Robert Koch Institute  Berlin Germany"},{"name":"German Centre for Infection Research Institute of Virology, Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin, Berlin Institute of Health  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrycja","family":"Klink","sequence":"additional","affiliation":[{"name":"Division of Viral Gastroenteritis and Hepatitis Pathogens and Enteroviruses, Department of Infectious Diseases Robert Koch Institute  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4632-525X","authenticated-orcid":false,"given":"Maximilian K.","family":"Nocke","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Virology Ruhr University Bochum  Bochum Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian\u2010Patrick","family":"Papp","sequence":"additional","affiliation":[{"name":"Division of Viral Gastroenteritis and Hepatitis Pathogens and Enteroviruses, Department of Infectious Diseases Robert Koch Institute  Berlin Germany"},{"name":"German Centre for Infection Research Institute of Virology, Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin, Berlin Institute of Health  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Harms","sequence":"additional","affiliation":[{"name":"Division of Viral Gastroenteritis and Hepatitis Pathogens and Enteroviruses, Department of Infectious Diseases Robert Koch Institute  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Kebelmann","sequence":"additional","affiliation":[{"name":"Division of Viral Gastroenteritis and Hepatitis Pathogens and Enteroviruses, Department of Infectious Diseases Robert Koch Institute  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Th\u00fcrmer","sequence":"additional","affiliation":[{"name":"Genome Sequencing, Methodology and Research Infrastructure Robert Koch Institute  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mira","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Intensive Medical Care Charit\u00e9 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britta","family":"Altmann","sequence":"additional","affiliation":[{"name":"Division of Viral Gastroenteritis and Hepatitis Pathogens and Enteroviruses, Department of Infectious Diseases Robert Koch Institute  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3564-1014","authenticated-orcid":false,"given":"Daniel","family":"Todt","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Virology Ruhr University Bochum  Bochum Germany"},{"name":"European Virus Bioinformatics Center (EVBC)  Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Hofmann","sequence":"additional","affiliation":[{"name":"German Centre for Infection Research Institute of Virology, Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin, Berlin Institute of Health  Berlin Germany"},{"name":"Labor Berlin, Charit\u00e9\u2010Vivantes GmbH  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2773-486X","authenticated-orcid":false,"given":"Claus\u2010Thomas","family":"Bock","sequence":"additional","affiliation":[{"name":"Division of Viral Gastroenteritis and Hepatitis Pathogens and Enteroviruses, Department of Infectious Diseases Robert Koch Institute  Berlin Germany"},{"name":"Institute of Tropical Medicine, University of Tuebingen  Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,1,13]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)61849-7"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/2049936119837162"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1099\/jgv.0.001778"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00705-022-05516-5"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.10.048"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2019.09.004"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0706992"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jceh.2013.05.003"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.02.050"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvh.13059"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24738"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01003-12"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035974"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01625-14"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00146-12"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvh.12157"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1018878108"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.03582-14"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.037259-0"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms8091417"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.00001"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-05706-w"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2018.03.005"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01686-17"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1099\/jgv.0.001435"},{"key":"e_1_2_12_27_1","unstructured":"HEV\u2010GLUE2019. Accessed May 12 2022.http:\/\/hev.glue.cvr.ac.uk\/#\/home."},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/msb.2011.75"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2604"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0178297"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr507"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu170"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp698"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr509"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1137\/141000671"},{"key":"e_1_2_12_36_1","volume-title":"R: A Language and Environment for Statistical Computing","author":"R Core Team","year":"2021"},{"key":"e_1_2_12_37_1","unstructured":"Pag\u00e8sH AboyounP GentlemanR DebRoyS.Biostrings: Efficient manipulation of biological strings. R package version 2.62.0.https:\/\/bioconductor.org\/packages\/Biostrings2021"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep39787"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1999.3310"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200300771"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2014.968875"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023505"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz268"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2014.08.017"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3600001"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.13.4586-4597.2003"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1097\/MEG.0b013e32834ca4da"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2016.06.010"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.17.8259"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.3390\/v13050762"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.15517","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/liv.15517","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.15517","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T20:16:00Z","timestamp":1692735360000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.15517"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,13]]},"references-count":49,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["10.1111\/liv.15517"],"URL":"https:\/\/doi.org\/10.1111\/liv.15517","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,13]]},"assertion":[{"value":"2022-09-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}