Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 23150796.
- Also identified by DOI 10.7554/eLife.00049 and PMC identifier 3485615.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.DOI:http://dx.doi.org/10.7554/eLife.00049.001.
Medical subject headings
- Hepatitis B virus
- Hepatitis Delta Virus
- Hepatocytes
- Organic Anion Transporters, Sodium-Dependent
- Receptors, Virus
- Symporters
- Viral Envelope Proteins