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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.

Original publication

DOI

10.1016/j.celrep.2016.09.084

Type

Journal article

Journal

Cell Rep

Volume

17

Pages

1357 - 1368

Keywords

NTCP, antiviral therapy, hepatitis B virus, hepatitis C virus, hepatitis D virus, host factor, innate immune responses, signaling, solute carrier, viral entry, Antiviral Agents, Bile Acids and Salts, Biological Transport, Cell Line, Tumor, Gene Expression Regulation, Gene Silencing, Hepacivirus, Hepatitis B Surface Antigens, Hepatitis B virus, Hepatitis C, Hepatitis Delta Virus, Hepatocytes, Humans, Immunity, Innate, Interferons, Organic Anion Transporters, Sodium-Dependent, Peptides, Protein Binding, Protein Precursors, Symporters, Virus Internalization