Highly diversified shrew hepatitis B viruses corroborate ancient origins and divergent infection patterns of mammalian hepadnaviruses

Proceedings of the National Academy of Sciences of the United States of America
Andrea RascheJan Felix Drexler

Abstract

Shrews, insectivorous small mammals, pertain to an ancient mammalian order. We screened 693 European and African shrews for hepatitis B virus (HBV) homologs to elucidate the enigmatic genealogy of HBV. Shrews host HBVs at low prevalence (2.5%) across a broad geographic and host range. The phylogenetically divergent shrew HBVs comprise separate species termed crowned shrew HBV (CSHBV) and musk shrew HBV (MSHBV), each containing distinct genotypes. Recombination events across host orders, evolutionary reconstructions, and antigenic divergence of shrew HBVs corroborated ancient origins of mammalian HBVs dating back about 80 million years. Resurrected CSHBV replicated in human hepatoma cells, but human- and tupaia-derived primary hepatocytes were resistant to hepatitis D viruses pseudotyped with CSHBV surface proteins. Functional characterization of the shrew sodium taurocholate cotransporting polypeptide (Ntcp), CSHBV/MSHBV surface peptide binding patterns, and infection experiments revealed lack of Ntcp-mediated entry of shrew HBV. Contrastingly, HBV entry was enabled by the shrew Ntcp. Shrew HBVs universally showed mutations in their genomic preCore domains impeding hepatitis B e antigen (HBeAg) production and resembling those o...Continue Reading

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Nov 26, 2018·Journal of Hepatology·Andrea RascheJan Felix Drexler
Mar 19, 2019·Virology·Fang-Yuan NieYong-Zhen Zhang

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Citations

Nov 12, 2020·American Journal of Physiology. Gastrointestinal and Liver Physiology·Kira A A T LowjagaJoachim Geyer
Mar 17, 2021·Proceedings of the National Academy of Sciences of the United States of America·Andrea RascheUNKNOWN Equid HBV Consortium
Mar 27, 2021·Virus Evolution·Wendy K JoJan Felix Drexler
Oct 5, 2021·Transboundary and Emerging Diseases·Wendy K JoJan Felix Drexler

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