Bats carry pathogenic hepadnaviruses antigenically related to hepatitis B virus and capable of infecting human hepatocytes

被引：143

作者：

Drexler, Jan Felix ^{[1
]}

Geipel, Andreas ^{[2
]}

Koenig, Alexander ^{[2
]}

Corman, Victor M. ^{[1
]}

van Riel, Debby ^{[3
]}

Leijten, Lonneke M. ^{[3
]}

Bremer, Corinna M. ^{[2
]}

Rasche, Andrea ^{[1
]}

Cottontail, Veronika M. ^{[4
,5
]}

Maganga, Gael D. ^{[6
]}

Schlegel, Mathias ^{[7
]}

Mueller, Marcel A. ^{[1
]}

Adam, Alexander ^{[8
]}

Klose, Stefan M. ^{[4
]}

Borges Carneiro, Aroldo Jose ^{[9
]}

Stoecker, Andreas ^{[10
]}

Franke, Carlos Roberto ^{[9
]}

Gloza-Rausch, Florian ^{[1
,11
]}

Geyer, Joachim ^{[12
]}

Annan, Augustina ^{[13
]}

Adu-Sarkodie, Yaw ^{[14
]}

Oppong, Samuel ^{[14
]}

Binger, Tabea ^{[1
]}

Vallo, Peter ^{[4
,15
]}

Tschapka, Marco ^{[4
,5
]}

Ulrich, Rainer G. ^{[7
]}

Gerlich, Wolfram H. ^{[2
]}

Leroy, Eric ^{[6
,16
]}

Kuiken, Thijs ^{[3
]}

Glebe, Dieter ^{[2
]}

Drosten, Christian ^{[1
]}

机构：

[1] Univ Bonn, Med Ctr, Inst Virol, D-53127 Bonn, Germany

[2] Univ Giessen, Inst Med Virol, D-35392 Giessen, Germany

[3] Erasmus MC, Depart Virosci, NL-3000 CA Rotterdam, Netherlands

[4] Univ Ulm, Inst Expt Ecol, D-89069 Ulm, Germany

[5] Smithsonian Trop Res Inst, Balboa Ancon, Panama

[6] Ctr Int Rech Med Franceville, Franceville, Gabon

[7] Friedrich Loeffler Inst, Inst Novel & Emerging Infect Dis, D-17493 Greifswald, Germany

[8] Univ Cologne, Med Ctr, Inst Pathol, D-50937 Cologne, Germany

[9] Univ Fed Bahia, Sch Vet Med, BR-40170110 Salvador, BA, Brazil

[10] Univ Fed Bahia, Univ Hosp Prof Edgard Santos, Infect Dis Res Lab, BR-40110060 Salvador, BA, Brazil

[11] Ctr Bat Protect & Informat, Noctalis, D-23795 Bad Segeberg, Germany

[12] Univ Giessen, Biomed Res Ctr, Inst Pharmacol & Toxicol, D-35392 Giessen, Germany

[13] Kumasi Ctr Collaborat Res Trop Med KCCR, Kumasi, Ghana

[14] Kwame Nkrumah Univ Sci & Technol, Fac Renewable Nat Resources, Kumasi, Ghana

[15] Acad Sci Czech Republic, Inst Vertebrate Biol, CS-60365 Brno, Czech Republic

[16] Univ Montpellier I, CNRS, IRD, UMR 224,MIVEGEC, F-34032 Rennes, France

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2013年 / 110卷 / 40期

关键词：

evolution; zoonosis; virome; metagenomics; reverse genetics; WOOLLY MONKEY; ENTRY; TRANSMISSION; GENOTYPES; PRIMATES; PROTEIN; SURFACE; ORIGIN; MICE; DNA;

D O I：

10.1073/pnas.1308049110

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：16151 / 16156

页数：6

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