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Advanced sequencing approaches detected insertions of viral and human origin in the viral genome of chronic hepatitis E virus patients

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dc.contributor.authorPapp, C-Patricken
dc.contributor.authorBiedermann, Paulaen
dc.contributor.authorHarms, Dominiken
dc.contributor.authorWang, Boen
dc.contributor.authorKebelmann, Marianneen
dc.contributor.authorChoi, Miraen
dc.contributor.authorHelmuth, Johannesen
dc.contributor.authorCorman, Victor M.en
dc.contributor.authorThuermer, Andreaen
dc.contributor.authorAltmann, Brittaen
dc.contributor.authorKlink, Patrycjaen
dc.contributor.authorHofmann, Joergen
dc.contributor.authorBock, C-Thomasen
dc.date.accessioned2022-08-02T13:08:38Zen
dc.date.available2022-08-02T13:08:38Zen
dc.date.issued2022-02-02en
dc.description.abstractThe awareness of hepatitis E virus (HEV) increased significantly in the last decade due to its unexpectedly high prevalence in high-income countries. There, infections with HEV-genotype 3 (HEV-3) are predominant which can progress to chronicity in immunocompromised individuals. Persistent infection and antiviral therapy can select HEV-3 variants; however, the spectrum and occurrence of HEV-3 variants is underreported. To gain in-depth insights into the viral population and to perform detailed characterization of viral genomes, we used a new approach combining long-range PCR with next-generation and third-generation sequencing which allowed near full-length sequencing of HEV-3 genomes. Furthermore, we developed a targeted ultra-deep sequencing approach to assess the dynamics of clinically relevant mutations in the RdRp-region and to detect insertions in the HVR-domain in the HEV genomes. Using this new approach, we not only identified several insertions of human (AHNAK, RPL18) and viral origin (RdRp-derived) in the HVR-region isolated from an exemplary sample but detected a variant containing two different insertions simultaneously (AHNAK- and RdRp-derived). This finding is the first HEV-variant recognized as such showing various insertions in the HVR-domain. Thus, this molecular approach will add incrementally to our current knowledge of the HEV-genome organization and pathogenesis in chronic hepatitis E.en
dc.description.notesOpen Access funding enabled and organized by Projekt DEAL. This research was funded by grants from the German Federal Ministry of Health (BMG) with regard to a decision of the German Bundestag by the Federal Government (CHED-project grant No: ZMVI1-2518FSB705). D.H. is supported by the Claussen-Simon-Stiftung (Claussen-Simon Foundation; CSF) "Dissertation Plus" program, Germany, and the Fazit-Stiftung "Promotions Stipendium". B.W. is supported by the China Scholarship Council (CSC), Beijing, China. B. A. is supported by ProFIT grant of the Investitionsbank Berlin (IBB, ProFIT No. 10169028, Berlin, Germany). The authors declare no conflict of interest. The funders BMG, CSF, Fazit, CSC, and ProFit had no role in the design of the study, in the collection, analyses or interpretation of data, in the writing of the manuscript, or in the decision to publish the results.en
dc.description.sponsorshipProjekt DEAL; German Federal Ministry of Health (BMG); Federal Government (CHED-project) [ZMVI1-2518FSB705]; Claussen-Simon-Stiftung (Claussen-Simon Foundation; CSF) "Dissertation Plus" program, Germany; Fazit-Stiftung "Promotions Stipendium"; China Scholarship Council (CSC), Beijing, China; ProFIT grant of the Investitionsbank Berlin (IBB, ProFIT, Berlin, Germany) [10169028]en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1038/s41598-022-05706-wen
dc.identifier.issn2045-2322en
dc.identifier.issue1en
dc.identifier.other1720en
dc.identifier.pmid35110582en
dc.identifier.urihttp://hdl.handle.net/10919/111419en
dc.identifier.volume12en
dc.language.isoenen
dc.publisherNature Portfolioen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectribavirin treatment failureen
dc.subjectpolyproline regionen
dc.subjectmutationsen
dc.subjectinfectionen
dc.subjectenglanden
dc.subjectgrowthen
dc.titleAdvanced sequencing approaches detected insertions of viral and human origin in the viral genome of chronic hepatitis E virus patientsen
dc.title.serialScientific Reportsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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