Journal Article

DKFZ-2026-00769

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Hepatitis E virus replication is maintained in proliferative cells within the intestinal crypt.

Prallet, S. ; Maier, N. ; Li, A. ; Afting, C. ; Huang, H.-E. ; Hu, J. ; Toprak, E. ; Keya, D. P. ; Colasanti, O. ; León-Janampa, N. ; Marlet, J. ; Beisel, C. ; Mogler, C. ; Puchas, P. ; Behrendt, P. ; Boettler, T. ; Steinmann, E. ; Saha, S. ; Laketa, V. ; Lohmann, V. ; Wittbrodt, J. ; Hermann, C. ; Dill, M.DKFZ* ; Dao Thi, V. L.

2026
Assoc. Washington, DC [u.a.]

Abstract: The hepatitis E virus (HEV) is a leading cause of acute hepatitis worldwide. Although most infections are self-limiting, zoonotic genotypes can persist in immunocompromised individuals. Transmitted via the fecal-oral route, HEV has been suggested to directly infect the intestinal epithelium, a tissue with high regenerative capacity. Here, we demonstrate that HEV predominantly infects proliferative transit-amplifying and intestinal stem cells within the crypts of human pluripotent stem cell-derived intestinal organoids (hIOs). Supporting this, we detected HEV RNA in the intestinal crypts of an HEV-infected patient. We further found that HEV infection spreads through cell division and is maintained in hIOs for more than 40 days, contrasting with acute hepatitis A virus, whose infections are rapidly cleared from hIOs. Given the self-renewal ability and metabolic constraints of proliferative intestinal progenitor cells, our findings suggest that intestinal crypts could serve as reservoirs for chronic HEV infection and highlight the intestinal crypt as a primary target for viral infection in the gastrointestinal tract.

Keyword(s): Hepatitis E virus: physiology (MeSH) ; Hepatitis E virus: genetics (MeSH) ; Humans (MeSH) ; Virus Replication (MeSH) ; Hepatitis E: virology (MeSH) ; Hepatitis E: pathology (MeSH) ; Organoids: virology (MeSH) ; Cell Proliferation (MeSH) ; Intestinal Mucosa: virology (MeSH) ; Stem Cells: virology (MeSH) ; RNA, Viral: genetics (MeSH) ; RNA, Viral

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Contributing Institute(s):

1. NWG Experimentelle Hepatologie, Entzündung und Krebs (D500)

Research Program(s):

1. 314 - Immunologie und Krebs (POF4-314) (POF4-314)

Appears in the scientific report 2026

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Database coverage:
; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

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