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Cynomolgus monkeys are successfully and persistently infected with hepatitis E virus genotype 3 (HEV-3) after

Noemi Rovaris Gardinali1, Juliana Rodrigues Guimarães1, Juliana Gil Melgaço1

  • 1Laboratório de Desenvolvimento Tecnológico em Virologia, Oswaldo Cruz, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.

Plos One
|March 23, 2017
PubMed

Insights

Hepatitis E virus genotype 3 (HEV-3) infection in immunosuppressed monkeys led to chronic hepatitis. Tacrolimus treatment exacerbated HEV-3 infection, causing liver damage without fibrosis, mimicking outcomes in human transplant recipients.

Area of Science:

  • Hepatology
  • Virology
  • Immunology

Background:

  • Hepatitis E virus genotype 3 (HEV-3) infection is linked to chronic hepatitis and cirrhosis in immunocompromised individuals.
  • The role of host immunosuppressive status in the development of HEV-related chronic hepatitis requires further investigation.

Purpose of the Study:

  • To investigate the relationship between immunosuppression induced by tacrolimus and the occurrence of HEV-3 related chronic hepatitis.
  • To establish a cause-effect relationship between HEV infection and tacrolimus treatment in a primate model.

Main Methods:

  • Cynomolgus monkeys were treated with tacrolimus to induce immunosuppression and subsequently infected with a Brazilian HEV-3 strain.
  • Monkeys were monitored for 160 days, assessing clinical signs, virological, biochemical, haematological parameters, and liver histopathology.
  • Tacrolimus blood levels were monitored to confirm sustained immunosuppression.

Main Results:

  • Immunosuppression was confirmed by clinical and laboratory findings, including opportunistic infections.
  • Chronic HEV infection was characterized by persistent viremia, viral shedding, and mild liver enzyme elevation.
  • Three out of four immunosuppressed monkeys developed chronic hepatitis with significant hepatocellular damage, steatosis, and inflammation, but without fibrosis or cirrhosis.

Conclusions:

  • Tacrolimus-immunosuppressed cynomolgus monkeys infected with HEV-3 exhibited severe hepatic lesions progressing to chronic hepatitis without fibrosis.
  • These findings mimic the liver pathology observed in tacrolimus-immunosuppressed solid organ transplant recipients.
  • The study confirmed a cause-effect relationship between HEV infection and tacrolimus treatment in this experimental model.

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