Integrin beta 1 facilitates non-enveloped hepatitis E virus cell entry through the recycling endosome

Rebecca Fu, Paula Jordan, Zoe Engels, Jasmin Alara Weihs, Josias Mürle, Huanting Chi, Sebastian Burbano de Lara, Barbara Helm, Mara Klöhn, Jungen Hu, Andrew Freistaedter, Tobias Boettler, Marco Binder, Ursula Klingmüller, Eike Steinmann, Pierre-Yves Lozach, Thibault Tubiana, Stanley M. Lemon and Viet Loan Dao Thi ()
Additional contact information
Rebecca Fu: Virology, Heidelberg University, Medical Faculty Heidelberg
Paula Jordan: Virology, Heidelberg University, Medical Faculty Heidelberg
Zoe Engels: Virology, Heidelberg University, Medical Faculty Heidelberg
Jasmin Alara Weihs: Virology, Heidelberg University, Medical Faculty Heidelberg
Josias Mürle: Virology, Heidelberg University, Medical Faculty Heidelberg
Huanting Chi: Partner Site Heidelberg
Sebastian Burbano de Lara: German Cancer Research Center (DKFZ)
Barbara Helm: German Cancer Research Center (DKFZ)
Mara Klöhn: Ruhr University Bochum
Jungen Hu: Virology, Heidelberg University, Medical Faculty Heidelberg
Andrew Freistaedter: Virology, Heidelberg University, Medical Faculty Heidelberg
Tobias Boettler: Medical Center – University of Freiburg
Marco Binder: German Cancer Research Center (DKFZ)
Ursula Klingmüller: German Cancer Research Center (DKFZ)
Eike Steinmann: Ruhr University Bochum
Pierre-Yves Lozach: IVPC
Thibault Tubiana: Université Paris-Saclay, CEA, CNRS
Stanley M. Lemon: The University of North Carolina at Chapel Hill
Viet Loan Dao Thi: Virology, Heidelberg University, Medical Faculty Heidelberg

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: Abstract Hepatitis E virus (HEV) is a major cause of acute hepatitis and mainly transmitted faecal-orally. HEV particles present in faeces are naked (nHEV), whereas those found in the blood are quasi-enveloped (eHEV) with a cell-derived lipid membrane. Despite its global health impact, the cellular life cycle of HEV remains poorly understood, particularly regarding the mechanisms of viral entry into host cells. To address this knowledge gap, we develop a high content RNA-FISH-based imaging assay that allows for the investigation of the entry pathways of both naked and quasi-enveloped HEV particles. Surprisingly, we find that integrin α3, previously implicated in nHEV cell entry, is not expressed in the cell types that are most permissive for HEV infection. Instead, we identify integrin β1 (ITGB1) pairing with different α-integrins as the key player mediating nHEV cell entry. Our results indicate that the interaction of nHEV with ITGB1 facilitates entry through Rab11-positive recycling endosomes. In contrast, eHEV particles do not interact with ITGB1 and enter cells using a classical endocytic route via Rab5a-positive early endosomes. The entry of both types of HEV particles requires endosomal acidification and proteolytic cleavage by lysosomal cathepsins, which ultimately results in delivery of the HEV genome to the cytoplasm.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-61071-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61071-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-61071-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().