Solute Carrier NTCP Regulates Innate Antiviral Immune Responses Targeting Hepatitis C Virus Infection of Hepatocytes

Cell Rep. 2016 Oct 25;17(5):1357-1368. doi: 10.1016/j.celrep.2016.09.084.


Chronic hepatitis B, C, and D virus (HBV, HCV, and HDV) infections are the leading causes of liver disease and cancer worldwide. Recently, the solute carrier and sodium taurocholate co-transporter NTCP has been identified as a receptor for HBV and HDV. Here, we uncover NTCP as a host factor regulating HCV infection. Using gain- and loss-of-function studies, we show that NTCP mediates HCV infection of hepatocytes and is relevant for cell-to-cell transmission. NTCP regulates HCV infection by augmenting the bile-acid-mediated repression of interferon-stimulated genes (ISGs), including IFITM3. In conclusion, our results uncover NTCP as a mediator of innate antiviral immune responses in the liver, and they establish a role for NTCP in the infection process of multiple viruses via distinct mechanisms. Collectively, our findings suggest a role for solute carriers in the regulation of innate antiviral responses, and they have potential implications for virus-host interactions and antiviral therapies.

Keywords: NTCP; antiviral therapy; hepatitis B virus; hepatitis C virus; hepatitis D virus; host factor; innate immune responses; signaling; solute carrier; viral entry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology*
  • Bile Acids and Salts / metabolism
  • Biological Transport
  • Cell Line, Tumor
  • Gene Expression Regulation / drug effects
  • Gene Silencing / drug effects
  • Hepacivirus / drug effects
  • Hepacivirus / physiology*
  • Hepatitis B Surface Antigens / metabolism
  • Hepatitis B virus / physiology
  • Hepatitis C / metabolism*
  • Hepatitis C / pathology
  • Hepatitis C / virology*
  • Hepatitis Delta Virus / physiology
  • Hepatocytes / drug effects
  • Hepatocytes / pathology
  • Hepatocytes / virology*
  • Humans
  • Immunity, Innate* / drug effects
  • Interferons / pharmacology
  • Organic Anion Transporters, Sodium-Dependent / metabolism*
  • Peptides / metabolism
  • Protein Binding / drug effects
  • Protein Precursors / metabolism
  • Symporters / metabolism*
  • Virus Internalization / drug effects


  • Antiviral Agents
  • Bile Acids and Salts
  • Hepatitis B Surface Antigens
  • Organic Anion Transporters, Sodium-Dependent
  • Peptides
  • Protein Precursors
  • Symporters
  • presurface protein 1, hepatitis B surface antigen
  • sodium-bile acid cotransporter
  • Interferons