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.
Highlights
2 billion people have been infected with human hepatitis B virus (HBV) worldwide
By using a synthetic modified peptide originating from the native aa 2–48 lipopeptide (Myr-47/ WT peptide (WT)) as a probe and employing a series of biochemical approaches and virological assays, we identified and confirmed that sodium taurocholate cotransporting polypeptide (NTCP), a multiple transmembrane transporter mainly expressed in the liver, interacts with the L proteins of HBV and hepatitis D virus (HDV) and functions as a common receptor for both viruses
HDV is an accepted surrogate for HBV entry, we further examined if exogenous expression of NTCP directly renders nonsusceptible cells susceptible to HBV infection
Summary
2 billion people have been infected with human hepatitis B virus (HBV) worldwide. Over 350 million people currently are chronically infected and are at high risk for progression to cirrhosis, liver failure, or cancer. More than 50% of liver cancers worldwide are attributed to HBV infection. HBV-related liver diseases remain a major public health problem, causing approximately 1 million deaths per year. Individuals coinfected with HBV and HDV are at greater risk for rapid progression and severe disease (Lavanchy, 2004; Hughes et al, 2011). Despite its enormous medical and social relevance, progress in HBV research has been impeded by the lack of understanding of HBV entry by which the virus infects human liver cells. The L protein and integrity of S protein are critical for HBV
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
