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Original research
Hepatitis E virus replication in human intestinal cells
  1. Olivier Marion1,2,3,
  2. Sebastien Lhomme2,3,4,
  3. Manon Nayrac2,
  4. Martine Dubois2,4,
  5. Mélanie Pucelle2,4,
  6. Mary Requena2,4,
  7. Marion Migueres2,4,
  8. Florence Abravanel2,3,4,
  9. Jean Marie Peron3,5,
  10. Nicolas Carrere3,6,
  11. Bertrand Suc3,6,
  12. Pierre Delobel2,3,7,
  13. Nassim Kamar1,2,3,
  14. Jacques Izopet2,3,4
  1. 1 Department of Nephrology and Organs Transplantation, Toulouse Rangueil University Hospital, Toulouse, France
  2. 2 INSERM UMR1043, Center for Pathophysiology of Toulouse Purpan, Toulouse, France
  3. 3 Paul Sabatier University, Toulouse, France
  4. 4 Virology Laboratory, National Reference Center for hepatitis E virus, Toulouse Purpan University Hospital, Toulouse, France
  5. 5 Hepatology and Gastroenterology Department, Toulouse Rangueil University Hospital, Toulouse, France
  6. 6 Digestive Surgery Department, Toulouse Rangueil University Hospital, Toulouse, France
  7. 7 Department of Infectious and Tropical Diseases, Toulouse Purpan University Hospital, Toulouse, France
  1. Correspondence to Professor Jacques Izopet, Virology Laboratory, National Reference Center for hepatitis E virus, Toulouse Purpan University Hospital, Toulouse, France; izopet.j{at}


Objective Hepatitis E virus (HEV), one of the most common agent of acute hepatitis worldwide, is mainly transmitted enterically, via contaminated water for HEV genotypes 1 (HEV1) and HEV2, or by eating raw or undercooked infected meat for HEV genotype 3 (HEV3) and HEV4. However, little is known about how the ingested HEV reaches the liver or its ability to replicate in intestinal cells.

Design We developed human primary cultures of small intestine epithelial cells and intestinal explants obtained from small bowel resections. The epithelial cells were also polarised on transwells. Cells were infected with Kernow-p6 strain or clinically derived virions.

Results Primary intestinal cells supported the growth of Kernow-p6 strain and HEV1 and HEV3 clinically derived virions. Polarised enterocytes infected with HEV1 and HEV3 strains released HEV particles vectorially: mostly into the apical compartment with a little basally. Iodixanol density gradient centrifugation of enterocyte-derived HEV virions gave bands at a density of 1.06–1.08 g/cm3, corresponding to that of quasi-enveloped HEV particles. Ribavirin therapy inhibited HEV excretion from the basal surface but not from the apical side of infected human enterocytes. HEV virions also infected intestinal tissue explants. Lastly, HEV RNA and antigen were detected in the intestinal crypts of a chronically infected patient.

Conclusion HEV can replicate in intestinal cells and reaches the liver as quasi-enveloped virions.

  • antiviral chemotherapy
  • enteric infections
  • epithelial cells
  • hepatitis E

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  • Contributors Virological workup: OM, SL, MN, MD, MP, MR, MM; collection of surgical samples: NC, BS, PD; data collection and statistical analyses: OM; paper preparation and review: OM, SL, FA, JMP, NK, JI; study design: OM, PD, NK, JI.

  • Funding Institut National de la Santé et de la Recherche Médicale (INSERM) UMR1043 operating grant.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval All procedures used complied with French law covering surgical waste and were approved by the local ethics committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.

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