Produção Nacional
Revisado por pares
A hepatitis B virus causes chronic infections in equids worldwide
2021; National Academy of Sciences; Volume: 118; Issue: 13 Linguagem: Inglês
10.1073/pnas.2013982118
ISSN1091-6490
AutoresAndrea Rasche, Felix Lehmann, Nora Goldmann, Michael Nagel, Andrés Moreira‐Soto, Daniel Nobach, Ianei de Oliveira Carneiro, Nikolaus Osterrieder, Alex D. Greenwood, Eike Steinmann, Alexander N. Lukashev, Gerhard Schüler, Dieter Glebe, Jan Felix Drexler, Álvaro Aguilar‐Setién, Walid Azab, Augusto Carluccio, Dimo Dietrich, Carlos Roberto Franke, Ignacio García‐Bocanegra, Fernando García‐Lacy, Lara M. Jeworoski, Joerg Jores, Ramona Kepper, Eduardo Martins Netto, Ellis Owusu‐Dabo, Jorge Raimundo Lins Ribas, Christina Roncoroni, Pia L. Roppert, Anton Rusenov, Nikolina Rusenova, Nikolay Sandev, Peter A. Seeber, Anat Shnaiderman‐Torban, Amir Steinman, Birthe Tegtmeyer, Vincenzo Veneziano, M.C. Veronesi, Stephanie Wälter, D. Zapryanova,
Tópico(s)Hepatitis Viruses Studies and Epidemiology
ResumoPreclinical 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.
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