Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus.
Elife
; 32012 Nov 13.
Article
em En
| MEDLINE
| ID: mdl-25409679
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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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Receptores Virais
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Vírus Delta da Hepatite
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Vírus da Hepatite B
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Transportadores de Ânions Orgânicos Dependentes de Sódio
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Simportadores
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article