Pathogenesis and transmission of hepatitis E virus (HEV) in pigs

Human hepatitis E virus (HEV) was first reported in 1980 and is now considered a major cause of acute non-A, non-B hepatitis in humans. HEV infection is reported throughout the world and occurs in epidemic form in developing countries where the disease is endemic and is often associated with water contamination after heavy rains or flooding. Sporadic human HEV infections occur in industrialized countries where infected individuals contract the infection while traveling to endemic regions. The fecal-oral route is considered the primary mode of HEV transmission in humans. HEV infection of pigs was discovered in 1997. Since 1997, sporadic HEV infections in industrialized countries have been reported in people who have not traveled abroad and are associated with HEV isolates genetically homologous to those found in domestic pigs. HEV infection of chickens and rats has since been documented in the U.S. and abroad.;Evidence suggests that pigs serve as an important reservoir for HEV and thus exposure to pigs, pork products, or pig organs may pose a risk of zoonotic or xenozoonotic infection. Swine HEV infection causes a subclinical, non-icteric hepatitis in growing pigs. Pigs experimentally-infected with swine HEV had no signs of clinical illness; however, they were viremic for 1 to 2 weeks, HEV was present in the liver of infected pigs, and the pigs shed a large amount of HEV in feces for several weeks. Similar results were demonstrated when pigs were infected with human HEV. We demonstrated that HEV infection of pregnant pigs does not induce reproductive failure. We also demonstrated that HEV could be transmitted by intravenous exposure of pigs to feces or liver collected from pigs in the early stages of infection. We subsequently demonstrated that a high dose and/or repeated exposure may be required for fecal-oral transmission of HEV and this is likely to be a common scenario in modern and traditional pig production facilities. HEV also can be detected in pig manure storage facilities such as concrete pits and earthen lagoons and we demonstrated that HEV found in the pit manure is viable and infectious to pigs. We attempted, but failed, to detect HEV in on-site drinking water or surface water on or near pig farms. These findings suggest a potential risk of contamination of water supplies by HEV in pig manure exists but evidence of this is lacking to date.;Cross-species infection with HEV among different species of animals has been demonstrated; swine HEV infects nonhuman primates, human HEV infects pigs, and chicken HEV infects turkeys. Swine and avian HEV have been shown to be genetically distant with nucleotide homology of approximately 60%. We demonstrated experimental infection of pigs with avian HEV. The avian HEV was found in the liver of inoculated pigs and was shed in feces for at least 3 weeks. Rat HEV failed to replicate in pigs. These findings further support the growing concern that pigs are an important reservoir of HEV and emphasize the critical role of pigs in the epidemiology of HEV

Comparison of PCR and a Swine Bioassay to Detect Hepatitis E Virus in Pig Tissues and Feces

Swine hepatitis E virus (HEV) was detected by a semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in liver tissue and feces but not in skeletal muscle, pancreas, or heart from pigs experimentally infected intravenously with swine hepatitis E virus (swine HEV). Homogenates of liver tissue and suspensions of feces prepared from swine HEV-infected pigs were inoculated intravenously into naïve pigs and induced infection. There was no evidence of transmission of swine HEV to pigs by intravenous route of inoculation with heart or pancreas, or oral route with skeletal muscle homogenates or fecal suspensions prepared from HEV-infected pigs. Results indicate that there is potential for transmission of swine HEV to naïve pigs, and potentially to humans, via pig liver or liver cell xenotransplantation. Failure to detect HEV by RT-PCR in muscle tissue and failure to transmit swine HEV via oral inoculation of muscle tissue suggests that the risk of transmission of HEV in pork meat products is minimal. The route of natural transmission of HEV is thought to be fecal-oral so the failure to transmit HEV via feces suggests that a very high infectious dose is necessary, or there are other routes of transmission. The semiquantitative RT-PCR assay correlates well with that of in vitro swine bioassay

Infection of Pigs with Avian Hepatitis E Virus (HEV)

It is now known that HEV can cross-species barriers. In the present study, we used a pig model to determine if HEV from chickens (avian HEV) or rats (rat HEV) was infectious to pigs. Thirty six, SPF pigs were randomly separated into 4 groups of 9 pigs each. Group 1 served as the sham-inoculated group. Group 2 was inoculated with rat HEV. Group 3 was inoculated with avian HEV. In the rat and avian HEV groups, 6 pigs were inoculated with the corresponding virus and 3 pigs remained uninoculated and served as contact controls. Group 4 was inoculated with the prototype swine HEV. Necropsy of 3 pigs from each group was performed on 7, 21, and 35 days postinoculation (dpi). In the rat and avian HEV groups, 2 inoculated and 1 contact control pigs were necropsied at each time point. Liver and bile from sham-inoculated pigs were negative for HEV throughout the study. Pigs in the sham and rat HEV group remained noninfected. Pigs inoculated with avian HEV and those inoculated with the swine HEV became viremic and shed HEV in feces. Both the avian and swine HEV infected pigs had mild-tomoderate lymphoplasmacytic hepatitis. The findings indicate that avian HEV is transmissible to pigs. This may open new areas of study in the epidemiology of HEV. Pigs may be an excellent model for comparative molecular and pathogenetic studies of different HEV strains

Experimental Inoculation of Growing Pigs with U.S. Strains of Swine and Human Hepatitis E Viruses

U.S. strains of swine and human hepatitis E viruses (HEV) are closely related genetically. We found that swine and human HEV differ in virulence and both induce subclinical, but morphologically discernable, hepatitis in experimentally infected SPF pigs. Experimental inoculation of pigs with human HEV may provide a useful model to study the pathogenesis of hepatitis E virus infection and test efficacy of human HEV vaccines

Detection of swine hepatitis E virus in the porcine hepatic lesion in Jeju Island

Swine hepatitis E virus (HEV) is an emerging zoonotic pathogen due to its close genomic similarity to human HEV. The prevalence of swine HEV in the hepatic lesion of pigs from the Jeju Island was investigated by reverse transcriptase polymerase chain reaction (RT-PCR). In total, 40 pigs with hepatitis lesions were selected from 19 different farms, based on examination by microscopy. RT-PCR findings revealed swine HEV in 22 cases (55%), including 18 suckling pigs and 4 growing pigs. Several histopathological lesions, including multifocal lymphoplasmacytic hepatitis, portal inflammation, and focal hepatocellular necrosis, were observed in liver sections of swine HEV PCR-positive pigs. The present study suggests that the prevalence of swine HEV is very high in the pig population in Jeju Island, and that pigs are infected at early stages of growth (under 2 months of age). The high prevalence of swine HEV in pigs in Jeju Island and the ability of this virus to infect across species puts people with swine-associated occupations at possible risk of zoonotic infection

Zoonotic hepatitis E: animal reservoirs and emerging risks

Hepatitis E virus (HEV) is responsible for enterically-transmitted acute hepatitis in humans with two distinct epidemiological patterns. In endemic regions, large waterborne epidemics with thousands of people affected have been observed, and, in contrast, in non-endemic regions, sporadic cases have been described. Although contaminated water has been well documented as the source of infection in endemic regions, the modes of transmission in non-endemic regions are much less known. HEV is a single-strand, positive-sense RNA virus which is classified in the Hepeviridae family with at least four known main genotypes (1–4) of mammalian HEV and one avian HEV. HEV is unique among the known hepatitis viruses, in which it has an animal reservoir. In contrast to humans, swine and other mammalian animal species infected by HEV generally remain asymptomatic, whereas chickens infected by avian HEV may develop a disease known as Hepatitis-Splenomegaly syndrome. HEV genotypes 1 and 2 are found exclusively in humans while genotypes 3 and 4 are found both in humans and other mammals. Several lines of evidence indicate that, in some cases involving HEV genotypes 3 and 4, animal to human transmissions occur. Furthermore, individuals with direct contact with animals are at higher risk of HEV infection. Cross-species infections with HEV genotypes 3 and 4 have been demonstrated experimentally. However, not all sources of human infections have been identified thus far and in many cases, the origin of HEV infection in humans remains unknown