Hepatitis E virus replication is maintained in proliferative cells within the intestinal crypt
- Sarah Prallet
- Niclas Maier
- Albert Li
- Cassian Afting
- Hao-En Huang
- Jungen Hu
- Elif Toprak
- Deb Purna Keya
- Ombretta Colasanti
- Nancy León-Janampa
- Julien Marlet
- Claudia Beisel
- Carolin Mogler
- Philip Puchas
- Patrick Behrendt
- Tobias Boettler
- Eike Steinmann
- Senjuti Saha
- Vibor Laketa
- Volker Lohmann
- Joachim Wittbrodt
- Carl Hermann
- Michael T. Dill
- Viet Loan Dao Thi
2026-04-01
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.