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The functional role of sodium taurocholate cotransporting polypeptide NTCP in the life cycle of hepatitis B, C and D viruses

Abstract

Chronic hepatitis B, C and D virus (HBV, HCV and HDV) infections are a major cause of liver disease and cancer worldwide. Despite employing distinct replication strategies, the three viruses are exclusively hepatotropic, and therefore depend on hepatocyte-specific host factors. The sodium taurocholate co-transporting polypeptide (NTCP), a transmembrane protein highly expressed in human hepatocytes that mediates the transport of bile acids, plays a key role in HBV and HDV entry into hepatocytes. Recently, NTCP has been shown to modulate HCV infection of hepatocytes by regulating innate antiviral immune responses in the liver. Here, we review the current knowledge of the functional role and the molecular and cellular biology of NTCP in the life cycle of the three major hepatotropic viruses, highlight the impact of NTCP as an antiviral target and discuss future avenues of research.

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Acknowledgements

This work was supported by Inserm, the University of Strasbourg, the European Union (ERC-2014-AdG-671231-HEPCIR, Infect-ERA hepBccc, EU H2020 Hep-CAR 667273), ANRS (2015/1099), the French Cancer Agency (ARC IHU201301187) and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number R03AI131066. CCC acknowledges fellowships from the Canadian Institutes of Health Research (201411MFE-338606-245517) and the Canadian Network on Hepatitis C. ERV is the recipient of an ANRS fellowship (ECTZ50121).

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CFE, LH, CCC, ERV, CS, TFB wrote the manuscript.

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Correspondence to Thomas F. Baumert.

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Eller, C., Heydmann, L., Colpitts, C.C. et al. The functional role of sodium taurocholate cotransporting polypeptide NTCP in the life cycle of hepatitis B, C and D viruses. Cell. Mol. Life Sci. 75, 3895–3905 (2018). https://doi.org/10.1007/s00018-018-2892-y

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Keywords

  • Liver cell biology
  • Bile acid transport
  • Host factor
  • Anti-viral therapy
  • Hepatocytes