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@ARTICLE{Fu:302284,
author = {R. Fu and P. Jordan and Z. Engels and J. A. Weihs and J.
Mürle and H. Chi and S. Burbano de Lara$^*$ and B. Helm$^*$
and M. Klöhn and J. Hu and A. Freistaedter and T. Boettler
and M. Binder$^*$ and U. Klingmüller$^*$ and E. Steinmann
and P.-Y. Lozach and T. Tubiana and S. M. Lemon and V. L.
Dao Thi},
title = {{I}ntegrin beta 1 facilitates non-enveloped hepatitis {E}
virus cell entry through the recycling endosome.},
journal = {Nature Communications},
volume = {16},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Springer Nature},
reportid = {DKFZ-2025-01303},
pages = {5403},
year = {2025},
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.},
keywords = {Endosomes: metabolism / Endosomes: virology / Virus
Internalization / Humans / Hepatitis E virus: physiology /
Hepatitis E virus: genetics / Integrin beta1: metabolism /
Integrin beta1: genetics / Hepatitis E: virology / Hepatitis
E: metabolism / rab5 GTP-Binding Proteins: metabolism / rab
GTP-Binding Proteins: metabolism / HEK293 Cells /
Cathepsins: metabolism / Lysosomes: metabolism / Cell Line /
Integrin beta1 (NLM Chemicals) / rab5 GTP-Binding Proteins
(NLM Chemicals) / Itgb1 protein, human (NLM Chemicals) /
rab11 protein (NLM Chemicals) / rab GTP-Binding Proteins
(NLM Chemicals) / Cathepsins (NLM Chemicals)},
cin = {B200 / D430},
ddc = {500},
cid = {I:(DE-He78)B200-20160331 / I:(DE-He78)D430-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40571699},
doi = {10.1038/s41467-025-61071-y},
url = {https://inrepo02.dkfz.de/record/302284},
}