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DOI10.1073/pnas.2013982118
A hepatitis B virus causes chronic infections in equids worldwide
Rasche A.; Lehmann F.; Goldmann N.; Nagel M.; Moreira-Soto A.; Nobach D.; de Oliveira Carneiro I.; Osterrieder N.; Greenwood A.D.; Steinmann E.; Lukashev A.N.; Schuler G.; Glebe D.; Drexler J.F.; the Equid HBV Consortium
发表日期2021
ISSN00278424
卷号118期号:13
英文摘要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. © 2021 National Academy of Sciences. All rights reserved.
英文关键词Animal model; Coinfection; Equids; Evolution; HBV
语种英语
scopus关键词hepatitis B antibody; hepatitis B surface antigen; hepatitis C antibody; sodium bile acid cotransporter; virus receptor; Africa; animal cell; animal experiment; animal model; animal tissue; antibody response; Article; biochemical analysis; chronic hepatitis B; controlled study; Deltavirus; domestication; donkey; Equidae; female; geographic distribution; Hepatitis B virus; Hepatitis C virus; histopathology; horizontal disease transmission; horse; host range; human; human cell; in vitro study; in vivo study; infection sensitivity; liver cell; liver injury; male; mixed infection; molecular evolution; nested polymerase chain reaction; nonhuman; preclinical study; priority journal; species difference; species identification; viral tropism; virus detection; virus entry; virus load; virus transmission; zebra
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/180115
作者单位Institute of Virology, Charité-Universitätsmedizin Berlin, Freie Universität Berlin and, Humboldt-Universität zu Berlin, Berlin, 10117, Germany; German Centre for Infection Research (DZIF), associated partner site Charité, Berlin, 10117, Germany; Institute of Medical Virology, National Reference Center for Hepatitis B Viruses and Hepatitis D Viruses, Justus Liebig University, Giessen, 35392, Germany; German Centre for Infection Research (DZIF), associated partner site Giessen-Marburg-Langen, Giessen, 35392, Germany; Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana; Institute of Veterinary Pathology, Justus Liebig University, Giessen, 35390, Germany; School of Veterinary Medicine, University Salvador (UNIFACS), Salvador, 41770-235, Brazil; Institute of Virology, Freie Universität Berlin, Berlin, 14163, Germany; Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong...
推荐引用方式
GB/T 7714
Rasche A.,Lehmann F.,Goldmann N.,et al. A hepatitis B virus causes chronic infections in equids worldwide[J],2021,118(13).
APA Rasche A..,Lehmann F..,Goldmann N..,Nagel M..,Moreira-Soto A..,...&the Equid HBV Consortium.(2021).A hepatitis B virus causes chronic infections in equids worldwide.Proceedings of the National Academy of Sciences of the United States of America,118(13).
MLA Rasche A.,et al."A hepatitis B virus causes chronic infections in equids worldwide".Proceedings of the National Academy of Sciences of the United States of America 118.13(2021).
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