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

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Verrier, Eloi R. | Colpitts, Che C. | Bach, Charlotte | Heydmann, Laura | Zona, Laetitia | Xiao, Fei | Thumann, Christine | Crouchet, Emilie | Gaudin, Raphaël | Sureau, Camille | François-Loïc, Cosset | Mckeating, Jane A. | Pessaux, Patrick | Hoshida, Yujin | Schuster, Catherine | Zeisel, Mirjam B. | Baumert, Thomas F.

Edité par CCSD ; Elsevier Inc -

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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