Evidence map›Paper›PMID 38844458›Full record

ArticleNature communications2024

Genetic determinants of host- and virus-derived insertions for hepatitis E virus replication.

Michael Hermann Wißing, Toni Luise Meister, Maximilian Klaus Nocke, André Gömer, Mejrema Masovic, Leonard Knegendorf, Yannick Brüggemann, Verian Bader, Anindya Siddharta, Claus-Thomas Bock and 7 more

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Proteasomal processing of the viral replicase ORF1 facilitates HEV-induced liver fibrosis.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Michael Hermann WißingDepartment for Molecular and Medical Medicine, Ruhr University Bochum, Bochum, Germany.
Toni Luise MeisterDepartment for Molecular and Medical Medicine, Ruhr University Bochum, Bochum, Germany.ORCID http://orcid.org/0000-0001-8962-9443
Maximilian Klaus NockeDepartment for Molecular and Medical Medicine, Ruhr University Bochum, Bochum, Germany.
André GömerDepartment for Molecular and Medical Medicine, Ruhr University Bochum, Bochum, Germany.
Mejrema MasovicDepartment for Molecular and Medical Medicine, Ruhr University Bochum, Bochum, Germany.
Leonard KnegendorfInstitute for Experimental Virology, TWINCORE Centre for Experimental and Clinical Infection Research, a Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.ORCID http://orcid.org/0000-0001-8469-1248
Yannick BrüggemannDepartment for Molecular and Medical Medicine, Ruhr University Bochum, Bochum, Germany.
Verian BaderDepartment of Molecular Cell Biology, Institute of Biochemistry and Pathobiochemistry, Ruhr University Bochum, Bochum, Germany.ORCID http://orcid.org/0000-0001-5260-4728
Anindya SiddhartaInstitute for Experimental Virology, TWINCORE Centre for Experimental and Clinical Infection Research, a Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
Claus-Thomas BockDivision of Viral Gastroenteritis and Hepatitis Pathogens and Enteroviruses, Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany.ORCID http://orcid.org/0000-0002-2773-486X
Alexander PlossDepartment of Molecular Biology, Princeton University, Princeton, NJ, USA.ORCID http://orcid.org/0000-0001-9322-7252
Scott P KenneyCenter for Food Animal Health, Departments of Animal Sciences and Veterinary Preventive Medicine, The Ohio State University, Wooster, OH, 43210, USA.
Konstanze F WinklhoferDepartment of Molecular Cell Biology, Institute of Biochemistry and Pathobiochemistry, Ruhr University Bochum, Bochum, Germany.
Patrick BehrendtInstitute for Experimental Virology, TWINCORE Centre for Experimental and Clinical Infection Research, a Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
Heiner WedemeyerDepartment of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Eike SteinmannDepartment for Molecular and Medical Medicine, Ruhr University Bochum, Bochum, Germany. Eike.Steinmann@ruhr-uni-bochum.de.ORCID http://orcid.org/0000-0002-3654-9965
Daniel TodtDepartment for Molecular and Medical Medicine, Ruhr University Bochum, Bochum, Germany. Daniel.Todt@ruhr-uni-bochum.de.ORCID http://orcid.org/0000-0002-3564-1014

Funding

Genetic Viral and Host Adaptations to Breach Species Barriers of HCVR01AI107301 · NIAID · PRINCETON UNIVERSITY · PI Thomas Pietschmann, Alexander Ploss · 2013 to 2026
$6.0M
Evaluating hepatitis E virus ribavirin resistance clinical outcomes in the immunosuppressed pig modelR21AI151736 · NIAID · OHIO STATE UNIVERSITY · PI JUNG, KWONIL, KENNEY, SCOTT P · 2021 to 2022
$410k
Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research) 01EK2106ABundesministerium für Bildung und Forschung (Federal Ministry of Education and Research) 01KI2106Bundesministerium für Gesundheit (Federal Ministry of Health, Germany) ZMVI1-2518FSB705Deutsche Forschungsgemeinschaft (German Research Foundation) 448974291Deutsche Forschungsgemeinschaft (German Research Foundation) 510558817Deutsche Forschungsgemeinschaft (German Research Foundation) INST 213/840-1 FUGGDeutsches Zentrum für Infektionsforschung (German Center for Infection Research) TTU 05.823_00NIAID NIH HHS R01 AI107301NIAID NIH HHS R21 AI151736
6 · The paper itself

Abstract

Hepatitis E virus (HEV) is a long-neglected RNA virus and the major causative agent of acute viral hepatitis in humans. Recent data suggest that HEV has a very heterogeneous hypervariable region (HVR), which can tolerate major genomic rearrangements. In this study, we identify insertions of previously undescribed sequence snippets in serum samples of a ribavirin treatment failure patient. These insertions increase viral replication while not affecting sensitivity towards ribavirin in a subgenomic replicon assay. All insertions contain a predicted nuclear localization sequence and alanine scanning mutagenesis of lysine residues in the HVR influences viral replication. Sequential replacement of lysine residues additionally alters intracellular localization in a fluorescence dye-coupled construct. Furthermore, distinct sequence patterns outside the HVR are identified as viral determinants that recapitulate the enhancing effect. In conclusion, patient-derived insertions can increase HEV replication and synergistically acting viral determinants in and outside the HVR are described. These results will help to understand the underlying principles of viral adaptation by viral- and host-sequence snatching during the clinical course of infection.

Indexed as

Hepatitis EHepatitis E virusRibavirinVirus ReplicationAntiviral AgentsGenome, ViralHumansMutagenesis, InsertionalRepliconRNA, ViralAntiviral AgentsRibavirinRNA, Viral

Identifiers

PMID38844458
PMCPMC11156872

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.