Yan Huan, Zhong Guocai, Xu Guangwei, He Wenhui, Jing Zhiyi, Gao Zhenchao, Huang Yi, Qi Yonghe, Peng Bo, Wang Haimin, Fu Liran, Song Mei, Chen Pan, Gao Wenqing, Ren Bijie, Sun Yinyan, Cai Tao, Feng Xiaofeng, Sui Jianhua, Li Wenhui
Graduate program in School of Life Sciences, Peking University, Beijing, China.
National Institute of Biological Sciences, Beijing, China.
Elife. 2012 Nov 13;3. doi: 10.7554/eLife.00049.
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.
人类乙型肝炎病毒（HBV）感染及HBV相关疾病仍是一个重大的公共卫生问题。同时感染其卫星病毒丁型肝炎病毒（HDV）的个体病情更为严重。两种病毒的细胞进入均由HBV包膜蛋白介导。大包膜蛋白的前S1结构域是受体结合的关键决定因素。然而，受体的身份尚不清楚。在此，我们通过使用近零距光交联和串联亲和纯化技术，揭示了前S1的受体结合区域与牛磺胆酸钠共转运多肽（NTCP）特异性相互作用，NTCP是一种主要在肝脏表达的多跨膜转运蛋白。沉默NTCP可抑制HBV和HDV感染，而外源性NTCP表达使原本不敏感的肝癌细胞对这些病毒感染变得敏感。此外，将无功能的猴NTCP的157 - 165位氨基酸替换为人源对应氨基酸后，赋予了其支持两种病毒感染的能力。我们的结果表明，NTCP是HBV和HDV的功能性受体。
