Hepatitis E virus replication in human intestinal cells

Autor: Sébastien Lhomme, Olivier Marion, Nicolas Carrere, Florence Abravanel, Marion Migueres, Nassim Kamar, Mélanie Pucelle, Pierre Delobel, Martine Dubois, Bertrand Suc, Mary Requena, Manon Nayrac, Jean-Marie Peron, Jacques Izopet
Přispěvatelé: Service de Néphrologie et transplantation d'organes CHU Rangueil TOULOUSE, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [Toulouse], CHU Toulouse [Toulouse], Service Hepato-Gastro-Enterologie, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées, Service de chirurgie digestive, Service des maladies infectieuses et tropicales [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse]
Rok vydání: 2019
Předmět:
0301 basic medicine
viruses
medicine.disease_cause
Virus Replication
MESH: Genotype
chemistry.chemical_compound
0302 clinical medicine
Hepatitis E virus
[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Genotype
Intestine
Small

MESH: Hepatocytes / drug effects
Cells
Cultured

Gastroenterology
virus diseases
Hepatitis E
3. Good health
MESH: Virus Replication / genetics
medicine.anatomical_structure
MESH: Epithelial Cells
RNA
Viral

030211 gastroenterology & hepatology
MESH: Cells
Cultured

Biology
Sensitivity and Specificity
03 medical and health sciences
MESH: Intestine
Small / cytology

Antigen
Ribavirin
medicine
Humans
MESH: RNA
Viral / genetics

Differential centrifugation
MESH: Humans
enteric infections
Epithelial Cells
MESH: Hepatitis E virus / genetics
medicine.disease
Virology
MESH: Sensitivity and Specificity
digestive system diseases
Small intestine
MESH: Hepatocytes / virology
030104 developmental biology
chemistry
MESH: Ribavirin / pharmacology
Hepatocytes
antiviral chemotherapy
hepatitis E
Explant culture
Zdroj: Gut
Gut, BMJ Publishing Group, 2020, 69 (5), pp.901-910. ⟨10.1136/gutjnl-2019-319004⟩
ISSN: 1468-3288
0017-5749
DOI: 10.1136/gutjnl-2019-319004⟩
Popis: ObjectiveHepatitis 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.DesignWe 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.ResultsPrimary 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.ConclusionHEV can replicate in intestinal cells and reaches the liver as quasi-enveloped virions.
Databáze: OpenAIRE