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

BMC Infectious Diseases

Marcelo A Pinto⁴  Oswaldo G Cruz⁷  Marcelo Pelajo-Machado⁹  Ana Carolina R A Cajaraville²  Julio Moran¹  Maria S Munné⁶  Jorge E González⁶  Wilhelmus HM Van der Poel³  Leilane M Lopes⁴  Vanessa S de Paula⁴  Jaqueline M de Oliveira⁴  Debora RL dos Santos⁵  Renato S Marchevsky⁸  Lilian G de Carvalho⁴ 

[1] Dr. Julio Moran Laboratories, Ebmatingen, Zurich, Switzerland;Laboratory of Virological Technology, Institute of Technology on Immunobiologicals, Bio-Manguinhos, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil;Central Veterinary, Institute of Wageningen University and Research Centre, Wageningen, The Netherlands;Laboratory of Technological Development in Virology, Oswaldo Cruz Institute/Oswaldo Cruz Foundation, Rio de Janeiro, Brazil;Laboratory of Veterinary Viruses, Department of Veterinary Microbiology and Immunology, UFRRJ, Rio de Janeiro, Brazil;National Reference Laboratory in Viral Hepatitis, National Institute of Infectious Diseases, Buenos Aires, Argentina;Programme of Scientific Computation, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil;Laboratory of Neurovirulence, Institute of Technology on Immunobiologicals, Bio-Manguinhos, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil;Laboratory of Pathology, Oswaldo Cruz Institute/Oswaldo Cruz Foundation, Rio de Janeiro, Brazil

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

Others  :  1145678
DOI  :  10.1186/1471-2334-13-495

 received in 2013-05-29, accepted in 2013-10-18,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 de Carvalho et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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