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
Affiliations
Huan Yan
Graduate program in School of Life Sciences, Peking University, Beijing, China; National Institute of Biological Sciences, Beijing, China
Guocai Zhong
National Institute of Biological Sciences, Beijing, China
Guangwei Xu
National Institute of Biological Sciences, Beijing, China
Wenhui He
National Institute of Biological Sciences, Beijing, China; Graduate program in Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Zhiyi Jing
National Institute of Biological Sciences, Beijing, China
Zhenchao Gao
Graduate program in School of Life Sciences, Peking University, Beijing, China; National Institute of Biological Sciences, Beijing, China
Yi Huang
National Institute of Biological Sciences, Beijing, China; Graduate program in Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Yonghe Qi
National Institute of Biological Sciences, Beijing, China
Bo Peng
National Institute of Biological Sciences, Beijing, China
Haimin Wang
National Institute of Biological Sciences, Beijing, China
Liran Fu
National Institute of Biological Sciences, Beijing, China; Graduate program in Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Mei Song
National Institute of Biological Sciences, Beijing, China; Graduate program in Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Pan Chen
National Institute of Biological Sciences, Beijing, China; Graduate program in Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Wenqing Gao
National Institute of Biological Sciences, Beijing, China
Bijie Ren
National Institute of Biological Sciences, Beijing, China
Yinyan Sun
National Institute of Biological Sciences, Beijing, China
Tao Cai
National Institute of Biological Sciences, Beijing, China
Xiaofeng Feng
National Institute of Biological Sciences, Beijing, China
Jianhua Sui
National Institute of Biological Sciences, Beijing, China
Wenhui Li
National Institute of Biological Sciences, Beijing, China
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.
