The hepatitis E virus capsid protein ORF2 counteracts cell-intrinsic antiviral responses to enable persistent replication in cell culture

Ann-Kathrin Mehnert; Sebastian Stegmaier; Carlos Ramirez Alvarez; Elif Toprak; Vladimir Gonçalves Magalhães; Carla Siebenkotten; Jungen Hu; Ana Luisa Costa; Daniel Kirrmaier; Michael Knop; Xianfang Wu; Thibault Tubiana; Carl Herrmann; Marco Binder; Viet Loan Dao Thi

doi:10.1371/journal.ppat.1013516

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Peer-reviewed

Research Article

The hepatitis E virus capsid protein ORF2 counteracts cell-intrinsic antiviral responses to enable persistent replication in cell culture

Ann-Kathrin Mehnert,

Roles Conceptualization, Formal analysis, Investigation, Methodology, Software, Writing – original draft, Writing – review & editing

Affiliations Schaller Research Group, Department of Infectious Diseases, Virology, Heidelberg University, Medical Faculty Heidelberg, Heidelberg, Germany, Heidelberg Biosciences International Graduate School (HBIGS), Heidelberg, Germany

https://orcid.org/0000-0001-8935-2894

⨯
Sebastian Stegmaier ,

Contributed equally to this work with: Sebastian Stegmaier, Carlos Ramirez Alvarez

Roles Formal analysis, Investigation, Methodology

Affiliations Faculty of Biosciences, Heidelberg University, Heidelberg, Germany, Research Group “Dynamics of Early Viral Infection and the Innate Antiviral Response”, Division Virus-Associated Carcinogenesis (D430), German Cancer Research Center (DKFZ), Heidelberg, Germany
⨯
Carlos Ramirez Alvarez ,

Contributed equally to this work with: Sebastian Stegmaier, Carlos Ramirez Alvarez

Roles Data curation, Formal analysis, Investigation, Methodology, Software

Affiliation Institute for Pharmacy and Molecular Biotechnology, Heidelberg University & BioQuant, Heidelberg, Germany
⨯
Elif Toprak,

Roles Methodology

Affiliations Schaller Research Group, Department of Infectious Diseases, Virology, Heidelberg University, Medical Faculty Heidelberg, Heidelberg, Germany, Heidelberg Biosciences International Graduate School (HBIGS), Heidelberg, Germany
⨯
Vladimir Gonçalves Magalhães,

Roles Methodology

Affiliation Research Group “Dynamics of Early Viral Infection and the Innate Antiviral Response”, Division Virus-Associated Carcinogenesis (D430), German Cancer Research Center (DKFZ), Heidelberg, Germany
⨯
Carla Siebenkotten,

Roles Methodology

Affiliation Schaller Research Group, Department of Infectious Diseases, Virology, Heidelberg University, Medical Faculty Heidelberg, Heidelberg, Germany
⨯
Jungen Hu,

Roles Formal analysis, Methodology

Affiliations Schaller Research Group, Department of Infectious Diseases, Virology, Heidelberg University, Medical Faculty Heidelberg, Heidelberg, Germany, Heidelberg Biosciences International Graduate School (HBIGS), Heidelberg, Germany
⨯
Ana Luisa Costa,

Roles Formal analysis, Methodology, Software

Affiliation Institute for Pharmacy and Molecular Biotechnology, Heidelberg University & BioQuant, Heidelberg, Germany
⨯
Daniel Kirrmaier,

Roles Resources

Affiliations Center for Molecular Biology of Heidelberg University (ZMBH), Heidelberg, Germany, Division Cell Morphogenesis and Signal Transduction (A260), German Cancer Research Center (DKFZ), Heidelberg, Germany
⨯
Michael Knop,

Roles Resources

Affiliations Center for Molecular Biology of Heidelberg University (ZMBH), Heidelberg, Germany, Division Cell Morphogenesis and Signal Transduction (A260), German Cancer Research Center (DKFZ), Heidelberg, Germany
⨯
Xianfang Wu,

Roles Resources

Affiliation Infection Biology Program and Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, United States of America
⨯
Thibault Tubiana,

Roles Data curation, Investigation, Software

Affiliation Institute for Integrative Biology of the Cell (I2BC), Université Paris-Saclay, CEA, CNRS, Gif-sur-Yvette, France
⨯
Carl Herrmann ,

Roles Data curation, Formal analysis, Supervision

* E-mail: Carl.Herrmann@uni-heidelberg.de (CH); VietLoan.DaoThi@med.uni-heidelberg.de (VLDT)

Affiliation German Center for Infection Research (DZIF), Partner Site Heidelberg, Heidelberg, Germany
⨯
Marco Binder,

Roles Supervision

Affiliation Research Group “Dynamics of Early Viral Infection and the Innate Antiviral Response”, Division Virus-Associated Carcinogenesis (D430), German Cancer Research Center (DKFZ), Heidelberg, Germany
⨯
Viet Loan Dao Thi

Roles Conceptualization, Formal analysis, Funding acquisition, Supervision, Writing – original draft, Writing – review & editing

* E-mail: Carl.Herrmann@uni-heidelberg.de (CH); VietLoan.DaoThi@med.uni-heidelberg.de (VLDT)

Affiliations Schaller Research Group, Department of Infectious Diseases, Virology, Heidelberg University, Medical Faculty Heidelberg, Heidelberg, Germany, German Center for Infection Research (DZIF), Partner Site Heidelberg, Heidelberg, Germany

https://orcid.org/0000-0003-2293-3592

⨯

The hepatitis E virus capsid protein ORF2 counteracts cell-intrinsic antiviral responses to enable persistent replication in cell culture

Ann-Kathrin Mehnert,
Sebastian Stegmaier,
Carlos Ramirez Alvarez,
Elif Toprak,
Vladimir Gonçalves Magalhães,
Carla Siebenkotten,
Jungen Hu,
Ana Luisa Costa,
Daniel Kirrmaier,
Michael Knop

Published: September 22, 2025
https://doi.org/10.1371/journal.ppat.1013516

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Update to S1 Table References

Posted by PLOS_Pathogens on 02 Dec 2025 at 19:30 GMT

The authors would like the clarify the following:

The references found in S1 Table are the following:
Wu, X. et al. Pan-Genotype Hepatitis E Virus Replication in Stem Cell-Derived Hepatocellular Systems. Gastroenterology 154, 663-674 e667, doi:10.1053/j.gastro.2017.10.041 (2018).
Wüst, S., Schad, P., Burkart, S. & Binder, M. Comparative Analysis of Six IRF Family Members in Alveolar Epithelial Cell-Intrinsic Antiviral Responses. Cells 10, doi:10.3390/cells10102600 (2021).
Hervouet, K. et al. An Arginine-Rich Motif in the ORF2 capsid protein regulates the hepatitis E virus lifecycle and interactions with the host cell. PLoS Pathog 18, e1010798, doi:10.1371/journal.ppat.1010798 (2022).

No competing interests declared.

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The hepatitis E virus capsid protein ORF2 counteracts cell-intrinsic antiviral responses to enable persistent replication in cell culture

The hepatitis E virus capsid protein ORF2 counteracts cell-intrinsic antiviral responses to enable persistent replication in cell culture

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Update to S1 Table References

Posted by PLOS_Pathogens on 02 Dec 2025 at 19:30 GMT