The results presented here strongly suggest that nude mice are susceptible to swine HEV as evidenced by viral antigen expression in liver and other extra-hepatic tissues, fecal viral shedding, hepatic lesions, and the presence of anti-HEV antibodies. The inoculated mice showed no clinical signs of HEV infection, as has been previously reported for other animal models, such as pigs and rats [14, 10, 31, 11, 18]. These findings reported here are helpful for the study of the replication mechanism, transmission and pathogenesis of HEV.
We first detected HEV RNA in the feces 4 days post-inoculation in agreement with previous findings in rats (4 day) , cynomolgus macaques (4–6 day)  and pigs (7 day) . In one of the contact-exposed nude mice, HEV RNA was first detected 7 days post-inoculation; i.e., 3 days later than in the directly inoculated mice. This delay reflected the lag time for virus to appear in the feces of the cohabiting inoculated mouse, and indicates that contact exposure infection occurred primarily by a fecal-oral route. In the liver, spleen, kidney, and colon of inoculated mice, HEV RNA was detected by RT-nPCR on day 4, 7, and 14, and HEV antigens were observed by indirect immunofluorescence. A large number of fluorescent of HEV antigen were observed in liver, spleen, and kidney, indicating these to be heavily infected tissues. Only a few suspected fluorescent HEV antigens were seen in the jejunum, ileum and colon [Figure 3]. This would indicate that HEV was probably replicating in these tissues, which is consistent with the previous studies , but this need to be further demonstrated with in situ hybridization. We detected HEV RNA in sera on day 4 and 7, but were unable to perform daily serum collection. In nonhuman primates and swine, the HEV RNA can be detected in bile , but it is not possible to obtain bile from a nude mouse owing to its small body size.
HEV infection in rats has been shown to have some aspects in common with HEV infection in nonhuman primates and swine; but one exception was that levels of ALT liver enzymes did not become elevated . In the current study, ALT levels in nude mice were also unchanged by HEV infection in nude mice. Aggarwal et al (2001) has confirmed that ALT elevation may not a useful indicator of HEV infection in primates . In contrast, the level of AST was significantly elevated in inoculated (2.6 fold) and contact exposed nude mice (1.6 fold). In addition, the sera of inoculated and contact exposed mice had elevated ALP activities, but no increases in TBIL were seen in response to HEV infection over the 21 days duration of the study.
The presence of HEV in stool can serve as a major source of transmission by contact exposure to other animals. In the current study, one of the contact-exposed mice became infected from viruses excreted by an inoculated nude mouse. This contact-exposed mouse also showed similar results to those shown by the inoculated nude mice, except that the anti-HEV antibody response was slower and AST liver enzyme levels were not as elevated. These findings are in agreement with a previous report of contact exposure in swine . Taken together, the data presented here show that HEV from swine can infect nude mice and that this infection can readily occur through fecal-oral transmission.