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A novel hepatitis B virus species discovered in capuchin monkeys sheds new light on the evolution of primate hepadnaviruses


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University of Bonn Medical Centre. Institute of Virology. Bonn, Germany / Federal University of Bahia. University Hospital Prof. Edgard Santos. Infectious Diseases Research Laboratory. Salvador BA, Brazil.

Justus Liebig University. Institute of Medical Virology. National Reference Center for Hepatitis B and D Viruses. Giessen, Germany / German Centre for Infection Research. Germany.

University of Bonn Medical Centre. Institute of Virology. Bonn, Germany / German Centre for Infection Research. Germany / Charit?-Universit?tsmedizin Berlin. Corporate member of Freie Universit?t Berlin. Humboldt-Universit?t zu Berlin / Berlin Institute of Health. Institute of Virology. Berlin, Germany.

Federal University of Bahia. School of Veterinary Medicine. Salvador, BA, Brazil.

Justus Liebig University. Institute of Medical Virology. National Reference Center for Hepatitis B and D Viruses. Giessen, Germany / German Centre for Infection Research. Germany.

University of Bonn Medical Centre. Institute of Virology. Bonn, Germany / German Centre for Infection Research. Germany / Charit?-Universit?tsmedizin Berlin. Corporate member of Freie Universit?t Berlin. Humboldt-Universit?t zu Berlin / Berlin Institute of Health. Institute of Virology. Berlin, Germany.

Justus Liebig University. Institute of Medical Virology. National Reference Center for Hepatitis B and D Viruses. Giessen, Germany / German Centre for Infection Research. Germany.

Justus Liebig University. Institute of Medical Virology. National Reference Center for Hepatitis B and D Viruses. Giessen, Germany / German Centre for Infection Research. Germany.

Justus Liebig University. Institute of Medical Virology. National Reference Center for Hepatitis B and D Viruses. Giessen, Germany / German Centre for Infection Research. Germany.

Justus Liebig University Giessen, Institute of Pharmacology and Toxicology. Biomedical Research Center Seltersberg. Schubertstr, Giessen, Germany.

University of Bonn. Institute for Biochemistry and Molecular Biology. Bonn, Germany.

Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Bel?m, PA, Brasil / University of S?o Paulo. Faculty of Veterinary Medicine and Animal Science. Department of Pathology. S?o Paulo, SP, Brazil.

University of S?o Paulo. Institute of Tropical Medicine and School of Medicine. Department of Gastroenterology. S?o Paulo, SP, Brazil.

University of Bonn Medical Centre. Institute of Virology. Bonn, Germany.

Federal University of Bahia. University Hospital Prof. Edgard Santos. Infectious Diseases Research Laboratory. Salvador, BA, Brazil.

University Hospital Freiburg. Department of Internal Medicine II/Molecular Biology. Hugstetter Str, Freiburg, Germany.

Federal University of Bahia. School of Veterinary Medicine. Salvador, BA, Brazil.

University of S?o Paulo. Institute of Tropical Medicine and School of Medicine. Department of Gastroenterology. S?o Paulo, SP, Brazil / Hospital Israelita Albert Einstein. S?o Paulo, SP, Brazil.

Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Bel?m, PA, Brazil.

Justus Liebig University Giessen. Institute of Pharmacology and Toxicology. Biomedical Research Center Seltersberg. Schubertstr, Giessen, Germany.

University of Leuven. Rega Institute, KU Leuven. Department of Microbiology and Immunology. Leuven, Belgium.

University of Bonn Medical Centre. Institute of Virology. Bonn, Germany / German Centre for Infection Research. Germany / Charit?-Universit?tsmedizin Berlin. Corporate member of Freie Universit?t Berlin. Humboldt-Universit?t zu Berlin / Berlin Institute of Health. Institute of Virology. Berlin, Germany.

Federal University of Bahia. University Hospital Prof. Edgard Santos. Infectious Diseases Research Laboratory. Salvador, BA, Brazil.

Justus Liebig University. Institute of Medical Virology. National Reference Center for Hepatitis B and D Viruses. Giessen, Germany / German Centre for Infection Research. Germany.

University of Bonn Medical Centre. Institute of Virology. Bonn, Germany / German Centre for Infection Research. Germany / Charit?-Universit?tsmedizin Berlin, Corporate member of Freie Universit?t Berlin. Humboldt-Universit?t zu Berlin / Berlin Institute of Health. Institute of Virology. Berlin, Germany.

All known hepatitis B virus (HBV) genotypes occur in humans and hominoid Old World nonhuman primates (NHP). The divergent Woolly Monkey HBV (WMHBV) forms another orthohepadnavirus species. The evolutionary origins of HBV are unclear. Methods: We analyzed sera from 124 Brazilian monkeys collected during 2012-2016 for hepadnaviruses using molecular and serological tools and conducted evolutionary analyses. Results: We identified a novel orthohepadnavirus species in capuchin monkeys (CMHBV). We found CMHBV-specific antibodies in five animals and high CMHBV concentrations in one animal. Non-inflammatory, probably chronic infection was consistent with an intact preCore domain, low genetic variability, core deletions in deep sequencing, and no elevated liver enzymes. Cross-reactivity of antisera against surface antigens suggested antigenic relatedness of HBV, CMHBV and WMHBV. Infection-determining CMHBV surface peptides bound to the human HBV receptor (hNTCP), but preferentially interacted with the capuchin monkey receptor homologue. CMHBV and WMHBV pseudotypes infected human hepatoma cells via the hNTCP and were poorly neutralized by HBV vaccine-derived antibodies, suggesting cross-species infections may be possible. Ancestral state reconstructions and sequence distance comparisons associated HBV with humans, whereas primate hepadnaviruses as a whole were projected to NHP ancestors. Co-phylogenetic analyses yielded evidence for co-speciation of hepadnaviruses and New World NHP. Bayesian hypothesis testing yielded strong support for an association of the HBV stem lineage with hominoid ancestors. Neither CMHBV, nor WMHBV were likely ancestors of the divergent human HBV genotypes F/H found in American natives. Conclusions: Our data suggest ancestral co-speciation of hepadnaviruses and NHP and an Old World origin of the divergent HBV genotypes F/H. Identification of a novel primate hepadnavirus offers new perspectives for urgently needed animal models of chronic hepatitis B.

Document Type Journal article
Language English
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