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

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

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

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 languageEnglish (US)
Pages (from-to)1357-1368
Number of pages12
JournalCell Reports
Volume17
Issue number5
DOIs
StatePublished - Oct 25 2016

Keywords

  • NTCP
  • antiviral therapy
  • hepatitis B virus
  • hepatitis C virus
  • hepatitis D virus
  • host factor
  • innate immune responses
  • signaling
  • solute carrier
  • viral entry

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Solute Carrier NTCP Regulates Innate Antiviral Immune Responses Targeting Hepatitis C Virus Infection of Hepatocytes'. Together they form a unique fingerprint.

  • Cite this

    Verrier, E. R., Colpitts, C. C., Bach, C., Heydmann, L., Zona, L., Xiao, F., Thumann, C., Crouchet, E., Gaudin, R., Sureau, C., Cosset, F. L., McKeating, J. A., Pessaux, P., Hoshida, Y., Schuster, C., Zeisel, M. B., & Baumert, T. F. (2016). Solute Carrier NTCP Regulates Innate Antiviral Immune Responses Targeting Hepatitis C Virus Infection of Hepatocytes. Cell Reports, 17(5), 1357-1368. https://doi.org/10.1016/j.celrep.2016.09.084