Breno Frederico de Carvalho Dominguez Souza1, Alexander König2, Andrea Rasche3, Ianei de Oliveira Carneiro4, Nora Stephan2, Victor Max Corman3, Pia Luise Roppert2, Nora Goldmann2, Ramona Kepper2, Simon Franz Müller5, Christof Völker6, Alex Junior Souza de Souza7, Michele Soares Gomes-Gouvêa8, Andrés Moreira-Soto9, Andreas Stöcker10, Michael Nassal11, Carlos Roberto Franke4, João Renato Rebello Pinho12, Manoel do Carmo Pereira Soares13, Joachim Geyer5, Philippe Lemey14, Christian Drosten3, Eduardo Martins Netto10, Dieter Glebe15, Jan Felix Drexler16. 1. Institute of Virology, University of Bonn Medical Centre, Bonn, Germany; University Hospital Prof. Edgard Santos, Infectious Diseases Research Laboratory, Federal University of Bahia, Salvador, Brazil. 2. Institute of Medical Virology, National Reference Center for Hepatitis B and D Viruses, Justus Liebig University, Giessen, Germany; German Centre for Infection Research (Deutsches Zentrum für Infektionsforschung), Berlin, Germany. 3. Institute of Virology, University of Bonn Medical Centre, Bonn, Germany; German Centre for Infection Research (Deutsches Zentrum für Infektionsforschung), Berlin, Germany; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Berlin, Germany. 4. School of Veterinary Medicine, Federal University of Bahia, Salvador, Brazil. 5. Institute of Pharmacology and Toxicology, Justus Liebig University Giessen, Biomedical Research Center Seltersberg, Giessen, Germany. 6. Institute for Biochemistry and Molecular Biology, University of Bonn, Bonn, Germany. 7. Evandro Chagas Institute, Hepatology Section, Belém, Brazil; Department of Pathology, Faculty of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil. 8. Institute of Tropical Medicine and School of Medicine, LIM07, Department of Gastroenterology, University of São Paulo, São Paulo, Brazil. 9. Institute of Virology, University of Bonn Medical Centre, Bonn, Germany; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Berlin, Germany. 10. University Hospital Prof. Edgard Santos, Infectious Diseases Research Laboratory, Federal University of Bahia, Salvador, Brazil. 11. Department of Internal Medicine II/Molecular Biology, University Hospital Freiburg, Freiburg, Germany. 12. Institute of Tropical Medicine and School of Medicine, LIM07, Department of Gastroenterology, University of São Paulo, São Paulo, Brazil; Hospital Israelita Albert Einstein, São Paulo, Brazil. 13. Evandro Chagas Institute, Hepatology Section, Belém, Brazil. 14. Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium. 15. Institute of Medical Virology, National Reference Center for Hepatitis B and D Viruses, Justus Liebig University, Giessen, Germany; German Centre for Infection Research (Deutsches Zentrum für Infektionsforschung), Berlin, Germany. Electronic address: Dieter.Glebe@viro.med.uni-giessen.de. 16. Institute of Virology, University of Bonn Medical Centre, Bonn, Germany; German Centre for Infection Research (Deutsches Zentrum für Infektionsforschung), Berlin, Germany; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Berlin, Germany. Electronic address: felix.drexler@charite.de.
Abstract
BACKGROUND & AIMS: All known hepatitis B virus (HBV) genotypes occur in humans and hominoid Old World non-human primates (NHPs). The divergent woolly monkey HBV (WMHBV) forms another orthohepadnavirus species. The evolutionary origins of HBV are unclear. METHODS: We analysed 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 (capuchin monkey hepatitis B virus [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 (human sodium taurocholate co-transporting polypeptide), but preferentially interacted with the capuchin monkey receptor homologue. CMHBV and WMHBV pseudotypes infected human hepatoma cells via the human sodium taurocholate co-transporting polypeptide, and were poorly neutralised by HBV vaccine-derived antibodies, suggesting that 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 was likely the ancestor 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. The identification of a novel primate hepadnavirus offers new perspectives for urgently needed animal models of chronic hepatitis B. LAY SUMMARY: The origins of HBV are unclear. The new orthohepadnavirus species from Brazilian capuchin monkeys resembled HBV in elicited infection patterns and could infect human liver cells using the same receptor as HBV. Evolutionary analyses suggested that primate HBV-related viruses might have emerged in African ancestors of New World monkeys millions of years ago. HBV was associated with hominoid primates, including humans and apes, suggesting evolutionary origins of HBV before the formation of modern humans. HBV genotypes found in American natives were divergent from those found in American monkeys, and likely introduced along prehistoric human migration. Our results elucidate the evolutionary origins and dispersal of primate HBV, identify a new orthohepadnavirus reservoir, and enable new perspectives for animal models of hepatitis B.
BACKGROUND & AIMS: All known hepatitis B virus (HBV) genotypes occur in humans and hominoid Old World non-human primates (NHPs). The divergent woolly monkeyHBV (WMHBV) forms another orthohepadnavirus species. The evolutionary origins of HBV are unclear. METHODS: We analysed 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 (capuchin monkey hepatitis B virus [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 humanHBV receptor (humansodium taurocholate co-transporting polypeptide), but preferentially interacted with the capuchin monkey receptor homologue. CMHBV and WMHBV pseudotypes infected humanhepatoma cells via the humansodium taurocholate co-transporting polypeptide, and were poorly neutralised by HBV vaccine-derived antibodies, suggesting that 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 was likely the ancestor of the divergent humanHBV 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. The identification of a novel primate hepadnavirus offers new perspectives for urgently needed animal models of chronic hepatitis B. LAY SUMMARY: The origins of HBV are unclear. The new orthohepadnavirus species from Brazilian capuchin monkeys resembled HBV in elicited infection patterns and could infect human liver cells using the same receptor as HBV. Evolutionary analyses suggested that primate HBV-related viruses might have emerged in African ancestors of New World monkeys millions of years ago. HBV was associated with hominoid primates, including humans and apes, suggesting evolutionary origins of HBV before the formation of modern humans. HBV genotypes found in American natives were divergent from those found in American monkeys, and likely introduced along prehistoric human migration. Our results elucidate the evolutionary origins and dispersal of primate HBV, identify a new orthohepadnavirus reservoir, and enable new perspectives for animal models of hepatitis B.
Authors: Andrea Rasche; Felix Lehmann; Nora Goldmann; Michael Nagel; Andres Moreira-Soto; Daniel Nobach; Ianei de Oliveira Carneiro; Nikolaus Osterrieder; Alex D Greenwood; Eike Steinmann; Alexander N Lukashev; Gerhard Schuler; Dieter Glebe; Jan Felix Drexler Journal: Proc Natl Acad Sci U S A Date: 2021-03-30 Impact factor: 11.205
Authors: Andrea Rasche; Felix Lehmann; Alexander König; Nora Goldmann; Victor M Corman; Andres Moreira-Soto; Andreas Geipel; Debby van Riel; Yulia A Vakulenko; Anna-Lena Sander; Hauke Niekamp; Ramona Kepper; Mathias Schlegel; Chantal Akoua-Koffi; Breno F C D Souza; Foday Sahr; Ayodeji Olayemi; Vanessa Schulze; Rasa Petraityte-Burneikiene; Andris Kazaks; Kira A A T Lowjaga; Joachim Geyer; Thijs Kuiken; Christian Drosten; Alexander N Lukashev; Elisabeth Fichet-Calvet; Rainer G Ulrich; Dieter Glebe; Jan Felix Drexler Journal: Proc Natl Acad Sci U S A Date: 2019-08-01 Impact factor: 11.205
Authors: Jaewon Yang; Alexander König; Soonju Park; Eunji Jo; Pil Soo Sung; Seung Kew Yoon; Eva Zusinaite; Denis Kainov; David Shum; Marc Peter Windisch Journal: JHEP Rep Date: 2021-04-30