Abstract
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.
Highlights
Hepatitis E virus (HEV) has been described as an emerging pathogen in Brazil and seems to be widely disseminated among swine herds
Out of the 3 animals that were inoculated with the Dutch swine HEV (D-swine), HEV RNA was detected at earlier time points in 2 (O1 and G3), with the virus being detected in the faeces at 5 or 7 dpi and in the sera at 7 to 14 dpi (Table 2)
Exceptions included monkeys X15 and F3, of which serum levels for Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) were higher compared with their respective pre-inoculation values and the cynomolgus standard normal values (Table 2)
Summary
Hepatitis 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. Infection with hepatitis E virus (HEV) has been well documented in endemic areas, such as southeastern and central Asia, the Middle East, the northern and western parts of Africa, and North America [1]. In Brazil, HEV genotype 3 seems to be widely disseminated. A retrospective study of sera from patients with non-A-C acute hepatitis from 2005–2009 led to the identification of the first autochthonous human case of acute HEV infection. The genetic relatedness of this strain and the genotype 3 HEV in pigs is indicative of the zoonotic circulation of HEV in Brazil [8,9,10]
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