A hepatitis B virus causes chronic infections in equids worldwide.
Abstract: Preclinical testing of novel therapeutics for chronic hepatitis B (CHB) requires suitable animal models. Equids host homologs of hepatitis C virus (HCV). Because coinfections of hepatitis B virus (HBV) and HCV occur in humans, we screened 2,917 specimens from equids from five continents for HBV. We discovered a distinct HBV species (Equid HBV, EqHBV) in 3.2% of donkeys and zebras by PCR and antibodies against EqHBV in 5.4% of donkeys and zebras. Molecular, histopathological, and biochemical analyses revealed that infection patterns of EqHBV resembled those of HBV in humans, including hepatotropism, moderate liver damage, evolutionary stasis, and potential horizontal virus transmission. Naturally infected donkeys showed chronic infections resembling CHB with high viral loads of up to 2.6 × 10 mean copies per milliliter serum for >6 mo and weak antibody responses. Antibodies against Equid HCV were codetected in 26.5% of donkeys seropositive for EqHBV, corroborating susceptibility to both hepatitis viruses. Deltavirus pseudotypes carrying EqHBV surface proteins were unable to infect human cells via the HBV receptor NTCP (Na/taurocholate cotransporting polypeptide), suggesting alternative viral entry mechanisms. Both HBV and EqHBV deltavirus pseudotypes infected primary horse hepatocytes in vitro, supporting a broad host range for EqHBV among equids and suggesting that horses might be suitable for EqHBV and HBV infections in vivo. Evolutionary analyses suggested that EqHBV originated in Africa several thousand years ago, commensurate with the domestication of donkeys. In sum, EqHBV naturally infects diverse equids and mimics HBV infection patterns. Equids provide a unique opportunity for preclinical testing of novel therapeutics for CHB and to investigate HBV/HCV interplay upon coinfection.
Publication Date: 2021-03-17 PubMed ID: 33723007PubMed Central: PMC8020657DOI: 10.1073/pnas.2013982118Google Scholar: Lookup
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Summary
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The study discusses the discovery of a novel hepatitis B virus that naturally infects donkeys and zebras, providing an animal model for testing treatments for chronic hepatitis B (CHB) in humans. The virus has similarities to human hepatitis B, such as liver targeting, moderate liver damage, and potential for horizontal transmission, and can also coexist with a form of hepatitis C.
Study on Hepatitis B Virus in Equids
- In this research, they tested nearly 3,000 specimens from donkeys and zebras from five continents for Hepatitis B Virus (HBV). They discovered a distinct species of HBV, termed as Equid HBV (EqHBV), in a small percentage of the population studied.
- Further examination revealed that the infection patterns of this new virus share similarities with human HBV. It primarily targets the liver, causes moderate liver damage, and shows potential for horizontal transmission (from one infected individual to another).
- Naturally infected donkeys showcased chronic infections resembling CHB with a high viral load, and weak antibody responses, which mimic the characteristics of human CHB.
Coexistence of Hepatitis B and Hepatitis C Viruses
- Investigations also found antibodies against Equid HCV in slightly over a quarter of donkeys that tested positive for EqHBV. This supports the possibility that both viruses can simultaneously infect their host, similarly to how HBV and HCV can co-infect humans.
Potential of Equids for Preclinical Testing
- The presence of HBV and Equid HCV in equids opens up the opportunity for these animals to be used as models in testing potential treatments for CHB before they are used in human trials.
- EqHBV deltavirus pseudotypes, which carry EqHBV surface proteins, were unable to infect human cells. However, both HBV and EqHBV deltavirus pseudotypes were successful in infecting primary horse hepatocytes in vitro, indicating equids can serve as hosts for these viruses, therefore providing a platform to further understand the diseases, their symptoms and potential cures.
Origin of Equid HBV
- The study suggests that EqHBV originated in Africa several thousand years ago, around the time when donkeys were being domesticated. This backs the understanding of the relationship between disease evolution and human civilization.
Cite This Article
APA
Rasche A, Lehmann F, Goldmann N, Nagel M, Moreira-Soto A, Nobach D, de Oliveira Carneiro I, Osterrieder N, Greenwood AD, Steinmann E, Lukashev AN, Schuler G, Glebe D, Drexler JF.
(2021).
A hepatitis B virus causes chronic infections in equids worldwide.
Proc Natl Acad Sci U S A, 118(13), e2013982118.
https://doi.org/10.1073/pnas.2013982118 Publication
Researcher Affiliations
- Institute of Virology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany.
- German Centre for Infection Research (DZIF), associated partner site Charité, 10117 Berlin, Germany.
- Institute of Medical Virology, National Reference Center for Hepatitis B Viruses and Hepatitis D Viruses, Justus Liebig University, 35392 Giessen, Germany.
- German Centre for Infection Research (DZIF), associated partner site Giessen-Marburg-Langen, 35392 Giessen, Germany.
- German Centre for Infection Research (DZIF), associated partner site Charité, 10117 Berlin, Germany.
- Institute of Medical Virology, National Reference Center for Hepatitis B Viruses and Hepatitis D Viruses, Justus Liebig University, 35392 Giessen, Germany.
- German Centre for Infection Research (DZIF), associated partner site Giessen-Marburg-Langen, 35392 Giessen, Germany.
- Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana.
- Institute of Virology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany.
- Institute of Veterinary Pathology, Justus Liebig University, 35390 Giessen, Germany.
- Institute of Virology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany.
- School of Veterinary Medicine, University Salvador (UNIFACS), 41770-235 Salvador, Brazil.
- Institute of Virology, Freie Universität Berlin, 14163 Berlin, Germany.
- Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong.
- Department of Wildlife Diseases, Leibniz Institute for Zoo and Wildlife Research, 10315 Berlin, Germany.
- Department of Veterinary Medicine, Freie Universität Berlin, 14163 Berlin, Germany.
- Faculty of Medicine, Department for Molecular and Medical Virology, Ruhr University Bochum, D-44801 Bochum, Germany.
- Martsinovsky Institute of Medical Parasitology, Tropical and Vector-Borne Diseases, Sechenov University, 119991 Moscow, Russia.
- Clinic for Obstetrics, Gynecology and Andrology of Large and Small Animals, Justus Liebig University Giessen, 35392 Giessen, Germany.
- Institute of Medical Virology, National Reference Center for Hepatitis B Viruses and Hepatitis D Viruses, Justus Liebig University, 35392 Giessen, Germany.
- German Centre for Infection Research (DZIF), associated partner site Giessen-Marburg-Langen, 35392 Giessen, Germany.
- Institute of Virology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany; felix.drexler@charite.de.
- German Centre for Infection Research (DZIF), associated partner site Charité, 10117 Berlin, Germany.
MeSH Terms
- Animals
- Antibodies, Viral / isolation & purification
- Antiviral Agents / pharmacology
- Antiviral Agents / therapeutic use
- Cell Line, Tumor
- Cells, Cultured
- Coinfection / drug therapy
- Coinfection / veterinary
- Coinfection / virology
- DNA, Viral / isolation & purification
- Disease Models, Animal
- Drug Evaluation, Preclinical / methods
- Equidae / virology
- Female
- Hepacivirus / genetics
- Hepacivirus / isolation & purification
- Hepacivirus / pathogenicity
- Hepatitis B virus / genetics
- Hepatitis B virus / immunology
- Hepatitis B virus / isolation & purification
- Hepatitis B virus / pathogenicity
- Hepatitis B, Chronic / blood
- Hepatitis B, Chronic / drug therapy
- Hepatitis B, Chronic / veterinary
- Hepatitis B, Chronic / virology
- Hepatitis C / drug therapy
- Hepatitis C / veterinary
- Hepatitis C / virology
- Hepatocytes
- Humans
- Liver / immunology
- Liver / pathology
- Liver / virology
- Primary Cell Culture
- Virus Internalization
Conflict of Interest Statement
The authors declare no competing interest.
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