TY - JOUR
T1 - A hepatitis B virus causes chronic infections in equids worldwide
AU - the Equid HBV Consortium
AU - Rasche, Andrea
AU - Lehmann, Felix
AU - Goldmann, Nora
AU - Nagel, Michael
AU - Moreira-Soto, Andres
AU - Nobach, Daniel
AU - de Oliveira Carneiro, Ianei
AU - Osterrieder, Nikolaus
AU - Greenwood, Alex D.
AU - Steinmann, Eike
AU - Lukashev, Alexander N.
AU - Schuler, Gerhard
AU - Glebe, Dieter
AU - Drexler, Jan Felix
AU - Aguilar-Setien, Alvaro
AU - Azab, Walid
AU - Carluccio, Augusto
AU - Dietrich, Dimo
AU - Franke, Carlos Roberto
AU - García-Bocanegra, Ignacio
AU - García-Lacy, Fernando
AU - Jeworoski, Lara M.
AU - Jores, Jörg
AU - Kepper, Ramona
AU - Netto, Eduardo Martins
AU - Owusu-Dabo, Ellis
AU - Ribas, Jorge R.L.
AU - Roncoroni, Christina
AU - Roppert, Pia L.
AU - Rusenov, Anton
AU - Rusenova, Nikolina
AU - Sandev, Nikolay
AU - Seeber, Peter A.
AU - Shnaiderman-Torban, Anat
AU - Steinman, Amir
AU - Tegtmeyer, Birthe
AU - Veneziano, Vincenzo
AU - Veronesi, Maria C.
AU - Walter, Stephanie
AU - Zapryanova, Dimitrinka
N1 - Publisher Copyright:
© 2021 National Academy of Sciences. All rights reserved.
PY - 2021/3/30
Y1 - 2021/3/30
N2 - Preclinical testing of novel therapeutics for chronic hepatitis B (CHB) requires suitable animal models. Equids host homologs of hepatitis C virus (HCV). Because coinfections of hepatitis B virus (HBV) and HCV occur in humans, we screened 2,917 specimens from equids from five continents for HBV. We discovered a distinct HBV species (Equid HBV, EqHBV) in 3.2% of donkeys and zebras by PCR and antibodies against EqHBV in 5.4% of donkeys and zebras. Molecular, histopathological, and biochemical analyses revealed that infection patterns of EqHBV resembled those of HBV in humans, including hepatotropism, moderate liver damage, evolutionary stasis, and potential horizontal virus transmission. Naturally infected donkeys showed chronic infections resembling CHB with high viral loads of up to 2.6 × 109 mean copies per milliliter serum for >6 mo and weak antibody responses. Antibodies against Equid HCV were codetected in 26.5% of donkeys seropositive for EqHBV, corroborating susceptibility to both hepatitis viruses. Deltavirus pseudotypes carrying EqHBV surface proteins were unable to infect human cells via the HBV receptor NTCP (Na+/taurocholate cotransporting polypeptide), suggesting alternative viral entry mechanisms. Both HBV and EqHBV deltavirus pseudotypes infected primary horse hepatocytes in vitro, supporting a broad host range for EqHBV among equids and suggesting that horses might be suitable for EqHBV and HBV infections in vivo. Evolutionary analyses suggested that EqHBV originated in Africa several thousand years ago, commensurate with the domestication of donkeys. In sum, EqHBV naturally infects diverse equids and mimics HBV infection patterns. Equids provide a unique opportunity for preclinical testing of novel therapeutics for CHB and to investigate HBV/ HCV interplay upon coinfection.
AB - Preclinical testing of novel therapeutics for chronic hepatitis B (CHB) requires suitable animal models. Equids host homologs of hepatitis C virus (HCV). Because coinfections of hepatitis B virus (HBV) and HCV occur in humans, we screened 2,917 specimens from equids from five continents for HBV. We discovered a distinct HBV species (Equid HBV, EqHBV) in 3.2% of donkeys and zebras by PCR and antibodies against EqHBV in 5.4% of donkeys and zebras. Molecular, histopathological, and biochemical analyses revealed that infection patterns of EqHBV resembled those of HBV in humans, including hepatotropism, moderate liver damage, evolutionary stasis, and potential horizontal virus transmission. Naturally infected donkeys showed chronic infections resembling CHB with high viral loads of up to 2.6 × 109 mean copies per milliliter serum for >6 mo and weak antibody responses. Antibodies against Equid HCV were codetected in 26.5% of donkeys seropositive for EqHBV, corroborating susceptibility to both hepatitis viruses. Deltavirus pseudotypes carrying EqHBV surface proteins were unable to infect human cells via the HBV receptor NTCP (Na+/taurocholate cotransporting polypeptide), suggesting alternative viral entry mechanisms. Both HBV and EqHBV deltavirus pseudotypes infected primary horse hepatocytes in vitro, supporting a broad host range for EqHBV among equids and suggesting that horses might be suitable for EqHBV and HBV infections in vivo. Evolutionary analyses suggested that EqHBV originated in Africa several thousand years ago, commensurate with the domestication of donkeys. In sum, EqHBV naturally infects diverse equids and mimics HBV infection patterns. Equids provide a unique opportunity for preclinical testing of novel therapeutics for CHB and to investigate HBV/ HCV interplay upon coinfection.
KW - Animal model
KW - Coinfection
KW - Equids
KW - Evolution
KW - HBV
UR - http://www.scopus.com/inward/record.url?scp=85102914477&partnerID=8YFLogxK
U2 - 10.1073/pnas.2013982118
DO - 10.1073/pnas.2013982118
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C2 - 33723007
AN - SCOPUS:85102914477
SN - 0027-8424
VL - 118
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 13
M1 - e2013982118
ER -
