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A bile acid transporter as a candidate receptor for hepatitis B and D virus entry.

Abstract : Human hepatitis B virus (HBV) infection and HBV-related diseases remain a major public health problem. Individuals coinfected with its satellite hepatitis D virus (HDV) have more severe disease. Cellular entry of both viruses is mediated by HBV envelope proteins. The pre-S1 domain of the large envelope protein is a key determinant for receptor(s) binding. However, the identity of the receptor(s) is unknown. Here, by using near zero distance photo-cross-linking and tandem affinity purification, we revealed that the receptor-binding region of pre-S1 specifically interacts with sodium taurocholate cotransporting polypeptide (NTCP), a multiple transmembrane transporter predominantly expressed in the liver. Silencing NTCP inhibited HBV and HDV infection, while exogenous NTCP expression rendered nonsusceptible hepatocarcinoma cells susceptible to these viral infections. Moreover, replacing amino acids 157-165 of nonfunctional monkey NTCP with the human counterpart conferred its ability in supporting both viral infections. Our results demonstrate that NTCP is a functional receptor for HBV and HDV.
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https://www.hal.inserm.fr/inserm-00850914
Contributor : Thomas Baumert <>
Submitted on : Friday, August 9, 2013 - 3:18:33 PM
Last modification on : Thursday, June 4, 2020 - 4:24:06 PM
Long-term archiving on: : Wednesday, April 5, 2017 - 8:35:34 PM

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Fei Xiao, Jane Mckeating, Thomas Baumert. A bile acid transporter as a candidate receptor for hepatitis B and D virus entry.. Journal of Hepatology, Elsevier, 2013, 58 (6), pp.1246-8. ⟨10.1016/j.jhep.2013.01.036⟩. ⟨inserm-00850914⟩

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