Hepatitis E virus (HEV) is the causative agent of acute hepatitis E in humans in developing\ncountries, but autochthonous cases of zoonotic genotype 3 (HEV-3) infection also occur in industrialized\ncountries. In contrast to swine, rats, and rabbits, natural HEV infections in mice have not yet been\ndemonstrated. The pig represents a well-established large animal model for HEV-3 infection, but a suitable\nsmall animal model mimicking natural HEV-3 infection is currently missing. Therefore, we experimentally\ninoculated C57BL/6 mice (wild-type, IFNAR-/-, CD4-/-, CD8-/-) and BALB/c nude (nu/nu) mice,\nWistar rats, and European rabbits with a wild boar-derived HEV-3 strain and monitored virus replication\nand shedding, as well as humoral immune responses. HEV RNA and anti-HEV antibodies were detected\nin one and two out of eight of the rats and all rabbits inoculated, respectively, but not in any of the mouse\nstrains tested. Remarkably, immunosuppressive dexamethasone treatment of rats did not enhance their\nsusceptibility to HEV infection. In rabbits, immunization with recombinant HEV-3 and ratHEV capsid\nproteins induced protection against HEV-3 challenge. In conclusion, the rabbit model for HEV-3 infection\nmay serve as a suitable alternative to the non-human primate and swine models, and as an appropriate\nbasis for vaccine evaluation studies.
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