title: Study of hepatitis E virus infection of genotype 1 and 3 in mice with humanised liver.
abstract: The hepatitis E virus (HEV) is responsible for approximately 20 million infections per year worldwide. Although most infected people can spontaneously clear an HEV infection, immune-compromised individuals may evolve towards chronicity. Chronic HEV infection can be cured using ribavirin, but viral isolates with low ribavirin sensitivity have recently been identified. Although some HEV isolates can be culturedin vitro, in vivostudies are essentially limited to primates and pigs. Since the use of these animals is hampered by financial, practical and/or ethical concerns, we evaluated if human liver chimeric mice could serve as an alternative.
  
  
  
  Humanised mice were inoculated with different HEV-containing preparations.
  
  
  
  Chronic HEV infection was observed after intrasplenic injection of cell culture-derived HEV, a filtered chimpanzee stool suspension and a patient-derived stool suspension. The viral load was significantly higher in the stool compared with the plasma. Overall, the viral titre in genotype 3-infected mice was lower than that in genotype 1-infected mice. Analysis of liver tissue of infected mice showed the presence of viral RNA and protein, and alterations in host gene expression. Intrasplenic injection of HEV-positive patient plasma and oral inoculation of filtered stool suspensions did not result in robust infection. Finally, we validated our model for the evaluation of novel antiviral compounds against HEV using ribavirin.
  
  
  
  Human liver chimeric mice can be infected with HEV of different genotypes. This small animal model will be a valuable tool for thein vivostudy of HEV infection and the evaluation of novel antiviral molecules.
authors.affiliation: Center for Vaccinology, Ghent University, Ghent, Belgium.|Microbiology and Immunology Department, Faculty of Medicine, Assuit University, Assuit, Egypt.
authors.forename: Ibrahim M
authors.initials: IM
authors.lastname: Sayed
authors.affiliation: Center for Vaccinology, Ghent University, Ghent, Belgium.
authors.forename: Lieven
authors.initials: L
authors.lastname: Verhoye
authors.affiliation: U1019-UMR 8204-CIIL-Centre d'Infection et d'Immunité de Lille, Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Cocquerel
authors.affiliation: INSERM U1043, IFR-BMT, CHU Purpan, Toulouse, France.|Université Paul-Sabatier, Toulouse, France.|Laboratory of Virology, CHU Purpan, Toulouse, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Abravanel
authors.affiliation: Center for Vaccinology, Ghent University, Ghent, Belgium.
authors.forename: Lander
authors.initials: L
authors.lastname: Foquet
authors.affiliation: U1019-UMR 8204-CIIL-Centre d'Infection et d'Immunité de Lille, Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Montpellier
authors.affiliation: Rega Institute, KUL, Leuven, Belgium.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Debing
authors.affiliation: Center for Vaccinology, Ghent University, Ghent, Belgium.
authors.forename: Ali
authors.initials: A
authors.lastname: Farhoudi
authors.affiliation: U1019-UMR 8204-CIIL-Centre d'Infection et d'Immunité de Lille, Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France.
authors.forename: Czeslaw
authors.initials: C
authors.lastname: Wychowski
authors.affiliation: U1019-UMR 8204-CIIL-Centre d'Infection et d'Immunité de Lille, Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Dubuisson
authors.affiliation: Center for Vaccinology, Ghent University, Ghent, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Leroux-Roels
authors.affiliation: Rega Institute, KUL, Leuven, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Neyts
authors.affiliation: INSERM U1043, IFR-BMT, CHU Purpan, Toulouse, France.|Université Paul-Sabatier, Toulouse, France.|Laboratory of Virology, CHU Purpan, Toulouse, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Izopet
authors.affiliation: de Duve Institute, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Michiels
authors.affiliation: Center for Vaccinology, Ghent University, Ghent, Belgium.
authors.forename: Philip
authors.initials: P
authors.lastname: Meuleman
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D004195:Disease Models, Animal; D015870:Gene Expression; D005838:Genotype; D016751:Hepatitis E / Q000188:drug therapy / Q000235:genetics / Q000821:virology*; D016752:Hepatitis E virus / Q000235:genetics*; D022781:Hepatocytes / Q000637:transplantation / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D008099:Liver / Q000737:chemistry*; D051379:Mice; D012367:RNA, Viral / Q000032:analysis*; D012254:Ribavirin / Q000627:therapeutic use; D018183:Transplantation Chimera; D019562:Viral Load; D014764:Viral Proteins / Q000032:analysis*
chemical_list: D000998:Antiviral Agents; D012367:RNA, Viral; D014764:Viral Proteins; D012254:Ribavirin
keywords: DRUG DEVELOPMENT; GENE EXPRESSION; GENOTYPE; HEPATITIS E; INFECTIOUS DISEASE