Abstract
Hepatitis E virus (HEV) is the causative agent of acute hepatitis E in humans in developing countries, but autochthonous cases of zoonotic genotype 3 (HEV-3) infection also occur in industrialized countries. In contrast to swine, rats, and rabbits, natural HEV infections in mice have not yet been demonstrated. The pig represents a well-established large animal model for HEV-3 infection, but a suitable small animal model mimicking natural HEV-3 infection is currently missing. Therefore, we experimentally inoculated C57BL/6 mice (wild-type, IFNAR−/−, CD4−/−, CD8−/−) and BALB/c nude (nu/nu) mice, Wistar rats, and European rabbits with a wild boar-derived HEV-3 strain and monitored virus replication and shedding, as well as humoral immune responses. HEV RNA and anti-HEV antibodies were detected in one and two out of eight of the rats and all rabbits inoculated, respectively, but not in any of the mouse strains tested. Remarkably, immunosuppressive dexamethasone treatment of rats did not enhance their susceptibility to HEV infection. In rabbits, immunization with recombinant HEV-3 and ratHEV capsid proteins induced protection against HEV-3 challenge. In conclusion, the rabbit model for HEV-3 infection may serve as a suitable alternative to the non-human primate and swine models, and as an appropriate basis for vaccine evaluation studies.
Highlights
Hepatitis E virus (HEV) is the causative agent of hepatitis E in humans and taxonomically classified in the family Hepeviridae
The HEV-3 strain used in this study originated from a liver sample of a naturally infected wild boar hunted in Northern Germany (Mecklenburg-Western Pomerania) in 2009, subtype 3b
Different C57BL/6 mouse strains were tested for susceptibility to HEV-3
Summary
Hepatitis E virus (HEV) is the causative agent of hepatitis E in humans and taxonomically classified in the family Hepeviridae. It is a small, quasi-enveloped virus with a single-stranded RNA genome of positive polarity [1,2,3]. Within the species Orthohepevirus A, human associated strains were grouped, namely genotypes 1 and 2 (HEV-1, HEV-2) that are restricted to humans and the zoonotic genotypes 3, 4 and 7 (HEV-3, HEV-4, HEV-7) that have been detected in domestic pig, wild boar, deer, and camels [7]. In Europe and Asia, food-borne zoonotic transmissions of HEV have been primarily associated with domestic pigs, wild boar, and deer as one of the main routes of human autochthonous infections [14,15,16]. HEV was thought to cause only acute courses, but especially
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