title: Experimental infection of rabbits with rabbit and genotypes 1 and 4 hepatitis E viruses.
abstract: BACKGROUND
  A recent study provided evidence that farmed rabbits in China harbor a novel hepatitis E virus (HEV) genotype. Although the rabbit HEV isolate had 77-79% nucleotide identity to the mammalian HEV genotypes 1 to 4, their genomic organization is very similar. Since rabbits are used widely experimentally, including as models of infection, we investigated whether they constitute an appropriate animal model for human HEV infection.
  
  
  METHODS
  Forty-two SPF rabbits were divided randomly into eleven groups and inoculated with six different isolates of rabbit HEV, two different doses of a second-passage rabbit HEV, and with genotype 1 and 4 HEV. Sera and feces were collected weekly after inoculation. HEV antigen, RNA, antibody and alanine aminotransferase in sera and HEV RNA in feces were detected. The liver samples were collected during necropsy subject to histopathological examination.
  
  
  RESULTS
  Rabbits inoculated with rabbit HEV became infected with HEV, with viremia, fecal virus shedding and high serum levels of viral antigens, and developed hepatitis, with elevation of the liver enzyme, ALT. The severity of disease corresponded to the infectious dose (genome equivalents), with the most severe hepatic disease caused by strain GDC54-18. However, only two of nine rabbits infected with HEV genotype 4, and none infected with genotype 1, developed hepatitis although six of nine rabbits inoculated with the genotype 1 HEV and in all rabbits inoculated with the genotype 4 HEV seroconverted to be positive for anti-HEV IgG antibody by 14 weeks post-inoculation.
  
  
  CONCLUSIONS
  These data indicate that rabbits are an appropriate model for rabbit HEV infection but are not likely to be useful for the study of human HEV. The rabbit HEV infection of rabbits may provide an appropriate parallel animal model to study HEV pathogenesis.
authors.affiliation: Department of Cellular Biology, National Institute for the Control of Pharmaceutical and Biological Products, Beijing, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Ma
authors.forename: Lin
authors.initials: L
authors.lastname: Zheng
authors.forename: Yunbo
authors.initials: Y
authors.lastname: Liu
authors.forename: Chenyan
authors.initials: C
authors.lastname: Zhao
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Harrison
authors.forename: Yuyuan
authors.initials: Y
authors.lastname: Ma
authors.forename: Shuhua
authors.initials: S
authors.lastname: Sun
authors.forename: Jingang
authors.initials: J
authors.lastname: Zhang
authors.forename: Youchun
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000097:blood; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005243:Feces / Q000821:virology; D005838:Genotype; D016751:Hepatitis E / Q000097:blood / Q000473:pathology / Q000821:virology*; D016752:Hepatitis E virus / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity; D006524:Hepatitis, Viral, Animal / Q000097:blood / Q000473:pathology / Q000821:virology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008099:Liver / Q000473:pathology / Q000821:virology; D012367:RNA, Viral / Q000235:genetics; D011817:Rabbits / Q000821:virology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D007074:Immunoglobulin G; D012367:RNA, Viral; D000410:Alanine Transaminase