Résumé
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.
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•NTCP is involved in hepatocyte infection by multiple viruses via distinct mechanisms•NTCP facilitates HCV infection by modulating innate antiviral responses•Solute carrier NTCP is a regulator of antiviral immune responses in the liver•This function is relevant for infection and therapies for hepatotropic viruses
Verrier et al. identify the sodium taurocholate co-transporter NTCP as a host factor regulating HCV infection. NTCP-mediated bile acid transport regulates innate responses targeting HCV infection. NTCP is a mediator of innate immunity and plays a role in the infection of multiple hepatotropic viruses.