title: Bats carry pathogenic hepadnaviruses antigenically related to hepatitis B virus and capable of infecting human hepatocytes.
abstract: The hepatitis B virus (HBV), family Hepadnaviridae, is one of most relevant human pathogens. HBV origins are enigmatic, and no zoonotic reservoirs are known. Here, we screened 3,080 specimens from 54 bat species representing 11 bat families for hepadnaviral DNA. Ten specimens (0.3%) from Panama and Gabon yielded unique hepadnaviruses in coancestral relation to HBV. Full genome sequencing allowed classification as three putative orthohepadnavirus species based on genome lengths (3,149-3,377 nt), presence of middle HBV surface and X-protein genes, and sequence distance criteria. Hepatic tropism in bats was shown by quantitative PCR and in situ hybridization. Infected livers showed histopathologic changes compatible with hepatitis. Human hepatocytes transfected with all three bat viruses cross-reacted with sera against the HBV core protein, concordant with the phylogenetic relatedness of these hepadnaviruses and HBV. One virus from Uroderma bilobatum, the tent-making bat, cross-reacted with monoclonal antibodies against the HBV antigenicity determining S domain. Up to 18.4% of bat sera contained antibodies against bat hepadnaviruses. Infectious clones were generated to study all three viruses in detail. Hepatitis D virus particles pseudotyped with surface proteins of U. bilobatum HBV, but neither of the other two viruses could infect primary human and Tupaia belangeri hepatocytes. Hepatocyte infection occurred through the human HBV receptor sodium taurocholate cotransporting polypeptide but could not be neutralized by sera from vaccinated humans. Antihepadnaviral treatment using an approved reverse transcriptase inhibitor blocked replication of all bat hepadnaviruses. Our data suggest that bats may have been ancestral sources of primate hepadnaviruses. The observed zoonotic potential might affect concepts aimed at eradicating HBV.
authors.affiliation: Institute of Virology, University of Bonn Medical Centre, 53127 Bonn, Germany.
authors.forename: Jan Felix
authors.initials: JF
authors.lastname: Drexler
authors.forename: Andreas
authors.initials: A
authors.lastname: Geipel
authors.forename: Alexander
authors.initials: A
authors.lastname: König
authors.forename: Victor M
authors.initials: VM
authors.lastname: Corman
authors.forename: Debby
authors.initials: D
authors.lastname: van Riel
authors.forename: Lonneke M
authors.initials: LM
authors.lastname: Leijten
authors.forename: Corinna M
authors.initials: CM
authors.lastname: Bremer
authors.forename: Andrea
authors.initials: A
authors.lastname: Rasche
authors.forename: Veronika M
authors.initials: VM
authors.lastname: Cottontail
authors.forename: Gael D
authors.initials: GD
authors.lastname: Maganga
authors.forename: Mathias
authors.initials: M
authors.lastname: Schlegel
authors.forename: Marcel A
authors.initials: MA
authors.lastname: Müller
authors.forename: Alexander
authors.initials: A
authors.lastname: Adam
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Klose
authors.forename: Aroldo José Borges
authors.initials: AJ
authors.lastname: Carneiro
authors.forename: Andreas
authors.initials: A
authors.lastname: Stöcker
authors.forename: Carlos Roberto
authors.initials: CR
authors.lastname: Franke
authors.forename: Florian
authors.initials: F
authors.lastname: Gloza-Rausch
authors.forename: Joachim
authors.initials: J
authors.lastname: Geyer
authors.forename: Augustina
authors.initials: A
authors.lastname: Annan
authors.forename: Yaw
authors.initials: Y
authors.lastname: Adu-Sarkodie
authors.forename: Samuel
authors.initials: S
authors.lastname: Oppong
authors.forename: Tabea
authors.initials: T
authors.lastname: Binger
authors.forename: Peter
authors.initials: P
authors.lastname: Vallo
authors.forename: Marco
authors.initials: M
authors.lastname: Tschapka
authors.forename: Rainer G
authors.initials: RG
authors.lastname: Ulrich
authors.forename: Wolfram H
authors.initials: WH
authors.lastname: Gerlich
authors.forename: Eric
authors.initials: E
authors.lastname: Leroy
authors.forename: Thijs
authors.initials: T
authors.lastname: Kuiken
authors.forename: Dieter
authors.initials: D
authors.lastname: Glebe
authors.forename: Christian
authors.initials: C
authors.lastname: Drosten
mesh_terms: D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D002685:Chiroptera / Q000821:virology*; D003429:Cross Reactions / Q000276:immunology; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D016678:Genome / Q000235:genetics; D015613:Hepadnaviridae / Q000235:genetics* / Q000472:pathogenicity*; D006515:Hepatitis B virus / Q000235:genetics; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D015151:Immunoblotting; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D014418:Tupaiidae; D015047:Zoonoses / Q000821:virology*
keywords: evolution; metagenomics; reverse genetics; virome; zoonosis
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