Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus

Huan Yan; Guocai Zhong; Guangwei Xu; Wenhui He; Zhiyi Jing; Zhenchao Gao; Yi Huang; Yonghe Qi; Bo Peng; Haimin Wang; Liran Fu; Mei Song; Pan Chen; Wenqing Gao; Bijie Ren; Yinyan Sun; Tao Cai; Xiaofeng Feng; Jianhua Sui; Wenhui Li

doi:10.7554/eLife.00049

Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus

Huan Yan, Guocai Zhong, Guangwei Xu, Wenhui He, Zhiyi Jing, Zhenchao Gao, Yi Huang, Yonghe Qi, Bo Peng, Haimin Wang, Liran Fu, Mei Song, Pan Chen, Wenqing Gao, Bijie Ren, Yinyan Sun, Tao Cai, Xiaofeng Feng, Jianhua Sui, Wenhui Li^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal Article › peer-review

1829 Citations (Scopus)

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.

Original language	English
Article number	e00049
Journal	eLife
Volume	2012
Issue number	1
DOIs	https://doi.org/10.7554/eLife.00049
Publication status	Published - 13 Nov 2012
Externally published	Yes

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10.7554/eLife.00049

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title = "Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus",

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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T1 - Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus

AU - Yan, Huan

AU - Zhong, Guocai

AU - Xu, Guangwei

AU - He, Wenhui

AU - Jing, Zhiyi

AU - Gao, Zhenchao

AU - Huang, Yi

AU - Qi, Yonghe

AU - Peng, Bo

AU - Wang, Haimin

AU - Fu, Liran

AU - Song, Mei

AU - Chen, Pan

AU - Gao, Wenqing

AU - Ren, Bijie

AU - Sun, Yinyan

AU - Cai, Tao

AU - Feng, Xiaofeng

AU - Sui, Jianhua

AU - Li, Wenhui

PY - 2012/11/13

Y1 - 2012/11/13

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/84879327902

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DO - 10.7554/eLife.00049

M3 - Journal Article

C2 - 23150796

AN - SCOPUS:84879327902

SN - 2050-084X

VL - 2012

JO - eLife

JF - eLife

IS - 1

M1 - e00049

ER -

Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus

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