The p.Ser267Phe variant of sodium taurocholate cotransporting polypeptide (NTCP) supports HBV infection with a low efficiency

Sodium taurocholate cotransporting polypeptide (NTCP) is a functional receptor for human hepatitis B virus (HBV) and its satellite virus Hepatitis D virus (HDV). Physiologically, NTCP is responsible for the majority of sodium-dependent bile acids uptake by hepatocytes. The p.Ser267Phe (S267F) variant of NTCP is a single nucleotide polymorphism (SNP) previously found to cause substantial loss of ability to support HBV and HDV infection and its taurocholic acid uptake function in vitro. Intriguingly, ten individuals were identified as S267F homozygotes in population studies of chronic hepatitis B (CHB) patients. In this study, we identified new HBV isolates from one homozygous S267F mutation carrier and confirmed new isolates also use wildtype-NTCP as a cellular receptor. Furthermore, we demonstrated S267F variant of NTCP, though inefficient, is still a functional receptor for HBV entry. This study advances our understanding of NTCP-mediated HBV infection.