Open Access Highly Accessed Research article

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

Lilian G de Carvalho14, Renato S Marchevsky2, Debora RL dos Santos3, Jaqueline M de Oliveira4, Vanessa S de Paula4, Leilane M Lopes4, Wilhelmus HM Van der Poel5, Jorge E González6, Maria S Munné6, Julio Moran7, Ana Carolina R A Cajaraville8, Marcelo Pelajo-Machado9, Oswaldo G Cruz10 and Marcelo A Pinto4*

Author Affiliations

1 Centre for Laboratory Animal Breeding, Department of Primatology, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil

2 Laboratory of Neurovirulence, Institute of Technology on Immunobiologicals, Bio-Manguinhos, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil

3 Laboratory of Veterinary Viruses, Department of Veterinary Microbiology and Immunology, UFRRJ, Rio de Janeiro, Brazil

4 Laboratory of Technological Development in Virology, Oswaldo Cruz Institute/Oswaldo Cruz Foundation, Rio de Janeiro, Brazil

5 Central Veterinary, Institute of Wageningen University and Research Centre, Wageningen, The Netherlands

6 National Reference Laboratory in Viral Hepatitis, National Institute of Infectious Diseases, Buenos Aires, Argentina

7 Dr. Julio Moran Laboratories, Ebmatingen, Zurich, Switzerland

8 Laboratory of Virological Technology, Institute of Technology on Immunobiologicals, Bio-Manguinhos, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil

9 Laboratory of Pathology, Oswaldo Cruz Institute/Oswaldo Cruz Foundation, Rio de Janeiro, Brazil

10 Programme of Scientific Computation, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil

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BMC Infectious Diseases 2013, 13:495  doi:10.1186/1471-2334-13-495

Published: 23 October 2013

Abstract

Background

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.

Methods

Six 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.

Results

Subclinical 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.

Conclusions

The 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.

Keywords:
Swine HEV; Human HEV; Lymphopenia; Fulminant hepatic failure; Genotype 3; Macaca fascicularis