Publikationsdatenbank

A hepatitis B virus causes chronic infections in equids worldwide (2021)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Rasche, Andrea

Lehmann, Felix

Goldmann, Nora

Nagel, Michael

Moreira-Soto, Andres

Nobach, Daniel

de Oliveira Carneiro, Ianei

Osterrieder, Nikolaus (WE 5)

Greenwood, Alex D. (WE 5)

Steinmann, Eike

Lukashev, Alexander N.

Schuler, Gerhard

Glebe, Dieter

Drexler, Jan Felix

Equid HBV Consortium

Quelle

Proceedings of the National Academy of Sciences of the United States of America

Bandzählung: 118

Heftzählung: 13

Seiten: Artikel e2013982118

ISSN: 1091-6490

Sprache

Englisch

Verweise

URL (Volltext): https://www.pnas.org/content/118/13/e2013982118

DOI: 10.1073/pnas.2013982118

Pubmed: 33723007

Kontakt

Institut für Virologie

Robert-von-Ostertag-Str. 7-13
14163 Berlin
+49 30 838 51833
virologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.