Experimental African HEV infection in cynomolgus macaques (Macaca fascicularis)

Cuyck-Gandre, H. Van; Cockman-Thomas, Rebecca A.; Caudill, Jeffrey D.; Asher, Ludmina S. V.; Armstrong, Karyn L.; Hauroeder, Barbel; Clements, Norma J.; Binn, Leonard N.; Longer, Charles F.

doi:10.1002/(sici)1096-9071(199807)55:3<197::aid-jmv3>3.0.co;2-x

Cited by 16 publications

(6 citation statements)

References 28 publications

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“…Specifically, when the vacuolar degeneration and fatty degeneration in hepatocytes is more pronounced, less ORF2 antigen is expressed. The characteristics of the experimental hepatitis E induced by HEV in rhesus monkeys showed similarities in this study, regardless of differences in the HEV genotypes used for infection, and did not differ from those in previous studies [Ticehurst et al, 1992;van Cuyck-Gandre et al, 1998].…”

Section: Discussionsupporting

confidence: 70%

Cross‐protection of hepatitis E virus genotypes 1 and 4 in rhesus macaques

Huang

Huayuan

Harrison

et al. 2008

Journal of Medical Virology

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The purpose of this study was to determine cross-protection between HEV genotypes 1 and 4, which are prevalent in China. Fecal suspensions of genotypes 1 and 4 from patients, as well as genotype 4 from swine, were inoculated intravenously into rhesus macaques. Each inoculum contained 5 x 10(4) genome equivalents of HEV. After infection, serum and fecal samples were collected serially and the levels of alanine aminotransferase (ALT) and anti-HEV IgG and IgM in sera, and HEV RNA in fecal samples, were measured. Liver biopsies were carried out. All the infected monkeys (12/12) developed anti-HEV IgG and exhibited fecal shedding of virus. IgM was detected in 11 of 12, and ALT elevation occurred about 2-6 weeks post-inoculation in 10 of 12, infected monkeys. Hepatic histopathology was consistent with acute viral hepatitis and the ORF2 antigen of HEV was detected in the granular cytoplasm of hepatocytes by immunohistochemistry. After recovery from their initial HEV infection, the monkeys were challenged with a heterologous genotype or heterologous source of HEV and monitored for hepatitis and fecal shedding. Previous infection with HEV completely or partially protected against subsequent challenge with a heterologous virus, because 7 of 11 monkeys did not develop HEV infection or shed virus in the feces, and none of them developed hepatitis or exhibited ALT elevation or liver biopsy findings of hepatitis. In conclusion, previous HEV infection may give rise to cross-genotype and cross-host-species protection.

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Section: Discussionsupporting

confidence: 70%

Cross‐protection of hepatitis E virus genotypes 1 and 4 in rhesus macaques

Huang

Huayuan

Harrison

et al. 2008

Journal of Medical Virology

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“…We observed that the first HEV-related event was viral shedding (at 5 to 21 dpi), as has been previously reported [32]. We assume that all of the animals presented with subclinical viral hepatitis independent of the source of the inoculum (swine or human) and the clinical presentation of the original host organism [22,31].…”

Section: Discussionsupporting

confidence: 63%

Infection by Brazilian and Dutch swine hepatitis E virus strains induces haematological changes in Macaca fascicularis

et al. 2013

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BackgroundHepatitis E virus (HEV) has been described as an emerging pathogen in Brazil and seems to be widely disseminated among swine herds. An autochthonous human case of acute hepatitis E was recently reported. To obtain a better understanding of the phenotypic profiles of both human and swine HEV strains, a experimental study was conducted using the animal model, Macaca fascicularis.MethodsSix cynomolgus monkeys (Macaca fascicularis) were inoculated intravenously with swine HEV genotype 3 that was isolated from naturally and experimentally infected pigs in Brazil and the Netherlands. Two other monkeys were inoculated with HEV genotype 3 that was recovered from Brazilian and Argentinean patients with locally acquired acute and fulminant hepatitis E. The haematological, biochemical, and virological parameters of all animals were monitored for 67 days.ResultsSubclinical hepatitis was observed in all monkeys after inoculation with HEV genotype 3 that was recovered from the infected swine and human patients. HEV RNA was detected in the serum and/or faeces of 6 out of the 8 cynomolgus monkeys between 5 and 53 days after inoculation. The mild inflammation of liver tissues and elevations of discrete liver enzymes were observed. Seroconversions to anti-HEV IgM and/or IgG were detected in 7 animals. Reactivities to anti-HEV IgA were also detected in the salivary samples of 3 animals. Interestingly, all of the infected monkeys showed severe lymphopenia and a trend toward monocytosis, which coincided with elevations in alanine aminotransferase and antibody titres.ConclusionsThe ability of HEV to cross the species barrier was confirmed for both the swine (Brazilian and Dutch) and human (Argentinean) strains, thus reinforcing the zoonotic risk of hepatitis E in South America. Cynomolgus monkeys that were infected with HEV genotype 3 developed subclinical hepatitis that was associated with haematological changes. Haematological approaches should be considered in future studies of HEV infection.

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“…However, the systemic distribution of HEV RNA and antigens is not yet well documented. Moreover, the route of experimental HEV infection in the past has been primarily by intravenous injection, which successfully infects certain animals, such as swine, BALB/c nude mice, and cynomolgus macaques [17]–[19]. However, the use of an intraperitoneal route for the infection of rabbits with HEV is rarely reported and its efficacy is still unclear.…”

Section: Introductionmentioning

confidence: 99%

Detection and Localization of Rabbit Hepatitis E Virus and Antigen in Systemic Tissues from Experimentally Intraperitoneally Infected Rabbits

et al. 2014

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Rabbit hepatitis E virus (HEV) is a novel genotype of HEV, and is considered to pose a risk of zoonotic transmission. Research into the systemic distribution of rabbit HEV in rabbits during different periods of infection has rarely been reported. To better understand this virus, we infected rabbits with second-passage rabbit HEV via an intraperitoneal route. After inoculation, the infection showed two types, temporary and constant infection. The detection of HEV RNA in the feces varied with time, and serum antigen correlated with fecal HEV RNA. Viremia only appeared 72 days after inoculation. The rabbits remained antibody negative throughout the experimental period. When HEV was localized, several organs besides the liver were HEV RNA positive. Tissue antigen was observed immunohistochemically in the different cells of various organs, especially in parts of the small intestine and the characteristic rabbit gut-associated lymphoid tissue. These data provide valuable information for future research into the pathogenesis of HEV.

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Experimental African HEV infection in cynomolgus macaques (Macaca fascicularis)

Cited by 16 publications

References 28 publications

Cross‐protection of hepatitis E virus genotypes 1 and 4 in rhesus macaques

Cross‐protection of hepatitis E virus genotypes 1 and 4 in rhesus macaques

Infection by Brazilian and Dutch swine hepatitis E virus strains induces haematological changes in Macaca fascicularis

Detection and Localization of Rabbit Hepatitis E Virus and Antigen in Systemic Tissues from Experimentally Intraperitoneally Infected Rabbits

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