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

Abstract 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.