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

Huan Yan(Peking University), Guocai Zhong(National Institute of Biological Sciences, Beijing), Guangwei Xu(National Institute of Biological Sciences, Beijing), Wenhui He(Chinese Academy of Medical Sciences & Peking Union Medical College), Zhiyi Jing(National Institute of Biological Sciences, Beijing), Zhenchao Gao(Peking University), Yi Huang(Chinese Academy of Medical Sciences & Peking Union Medical College), Yonghe Qi(National Institute of Biological Sciences, Beijing), Xiaozhong Peng(National Institute of Biological Sciences, Beijing), Haimin Wang(National Institute of Biological Sciences, Beijing), Liran Fu(Chinese Academy of Medical Sciences & Peking Union Medical College), Mei Song(Chinese Academy of Medical Sciences & Peking Union Medical College), Pan Chen(Chinese Academy of Medical Sciences & Peking Union Medical College), Wenqing Gao(National Institute of Biological Sciences, Beijing), Bijie Ren(National Institute of Biological Sciences, Beijing), Yinyan Sun(National Institute of Biological Sciences, Beijing), Tao Cai(National Institute of Biological Sciences, Beijing), Xiaofeng Feng(National Institute of Biological Sciences, Beijing), Jianhua Sui(National Institute of Biological Sciences, Beijing), Wenhui Li(National Institute of Biological Sciences, Beijing)
eLife
November 13, 2012
10.7554/elife.00049
Cited by 2,093Open Access
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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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