Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus
By Huan Yan, Guocai Zhong, Guangwei Xu, Wenhui He, Zhiyi Jing, Zhenchao Gao, Yi Huang, Yonghe Qi, B. Peng, Haimin Wang and 10 more. eLife, 2012
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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. DOI: http://dx.doi.org/10.7554/eLife.00049.001
Subfields: Epidemiology, Oncology
View Paper: https://www.semanticscholar.org/paper/931fd1794f750ed192ad7abf8b3e0f78cd1c2a1d
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Citations in the corpus
- Molecular Biology of Hepatitis B Virus Infection (2015, positive): “Building on this information, Li and colleagues (Yan et al., 2012) used the myristylated preS1-derived peptide to isolate receptor candidates expressed in primary hepatocytes cultures derived from tree shrews, which can be infected with HBV and HDV.”
- HBV cccDNA: viral persistence reservoir and key obstacle for a cure of chronic hepatitis B (2015, background): “8 9 Longer-term HBV susceptibility can be achieved by xenotrans-planting human or tupaia hepatocytes into immunode fi cient mice 58 59 but is technically very elaborate.”