Drexler, Jan Felix ORCID: 0000-0002-3509-0232, Geipel, Andreas, Koenig, Alexander, Corman, Victor M., van Riel, Debby ORCID: 0000-0001-9753-3564, Leijten, Lonneke M., Bremer, Corinna M., Rasche, Andrea ORCID: 0000-0001-6693-1180, Cottontail, Veronika M., Maganga, Gael D., Schlegel, Mathias, Mueller, Marcel A., Adam, Alexander, Klose, Stefan M., Borges Carneiro, Aroldo Jose, Stoecker, Andreas, Franke, Carlos Roberto ORCID: 0000-0001-5253-8150, Gloza-Rausch, Florian, Geyer, Joachim, Annan, Augustina, Adu-Sarkodie, Yaw, Oppong, Samuel, Binger, Tabea, Vallo, Peter, Tschapka, Marco, Ulrich, Rainer G., Gerlich, Wolfram H., Leroy, Eric, Kuiken, Thijs ORCID: 0000-0001-5501-9049, Glebe, Dieter and Drosten, Christian (2013). Bats carry pathogenic hepadnaviruses antigenically related to hepatitis B virus and capable of infecting human hepatocytes. Proc. Natl. Acad. Sci. U. S. A., 110 (40). S. 16151 - 16157. WASHINGTON: NATL ACAD SCIENCES. ISSN 0027-8424

Full text not available from this repository.

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Drexler, Jan FelixUNSPECIFIEDorcid.org/0000-0002-3509-0232UNSPECIFIED
Geipel, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koenig, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Corman, Victor M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Riel, DebbyUNSPECIFIEDorcid.org/0000-0001-9753-3564UNSPECIFIED
Leijten, Lonneke M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bremer, Corinna M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rasche, AndreaUNSPECIFIEDorcid.org/0000-0001-6693-1180UNSPECIFIED
Cottontail, Veronika M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maganga, Gael D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schlegel, MathiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller, Marcel A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Adam, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klose, Stefan M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Borges Carneiro, Aroldo JoseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stoecker, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Franke, Carlos RobertoUNSPECIFIEDorcid.org/0000-0001-5253-8150UNSPECIFIED
Gloza-Rausch, FlorianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Geyer, JoachimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Annan, AugustinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Adu-Sarkodie, YawUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oppong, SamuelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Binger, TabeaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vallo, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tschapka, MarcoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ulrich, Rainer G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gerlich, Wolfram H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leroy, EricUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kuiken, ThijsUNSPECIFIEDorcid.org/0000-0001-5501-9049UNSPECIFIED
Glebe, DieterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Drosten, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-475501
DOI: 10.1073/pnas.1308049110
Journal or Publication Title: Proc. Natl. Acad. Sci. U. S. A.
Volume: 110
Number: 40
Page Range: S. 16151 - 16157
Date: 2013
Publisher: NATL ACAD SCIENCES
Place of Publication: WASHINGTON
ISSN: 0027-8424
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
WOOLLY MONKEY; ENTRY; TRANSMISSION; GENOTYPES; PRIMATES; PROTEIN; SURFACE; ORIGIN; MICE; DNAMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/47550

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item