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

doi:10.1016/j.celrep.2016.09.084

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

Immunology and Immunotherapy

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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 language	English
Pages (from-to)	1357-1368
Number of pages	12
Journal	Cell Reports
Volume	17
Issue number	5
DOIs	https://doi.org/10.1016/j.celrep.2016.09.084
Publication status	Published - 25 Oct 2016

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Verrier_et_al_Solute_carrier_NTCP_regulates_Cell_Reports_2016
Checked for eligibility: 19/01/2016
Final published version, 2.82 MBLicence: Creative Commons: Attribution-NonCommercial-NoDerivs (CC BY-NC-ND)

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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

@article{1f408e01cbcd4be3b274f035eafeaa7a,

title = "Solute carrier NTCP regulates innate antiviral immune responses targeting Hepatitis C virus infection of hepatocytes",

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.",

author = "Verrier, {Eloi R} and Colpitts, {Che C} and Charlotte Bach and Laura Heydmann and Laetitia Zona and Fei Xiao and Christine Thumann and Emilie Crouchet and Rapha{\"e}l Gaudin and Camille Sureau and Fran{\c c}ois-Lo{\"i}c Cosset and McKeating, {Jane A} and Patrick Pessaux and Yujin Hoshida and Catherine Schuster and Zeisel, {Mirjam B} and Baumert, {Thomas F}",

year = "2016",

month = oct,

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doi = "10.1016/j.celrep.2016.09.084",

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Verrier, ER, Colpitts, CC, Bach, C, Heydmann, L, Zona, L, Xiao, F, Thumann, C, Crouchet, E, Gaudin, R, Sureau, C, Cosset, F-L, McKeating, JA, Pessaux, P, Hoshida, Y, Schuster, C, Zeisel, MB & Baumert, TF 2016, 'Solute carrier NTCP regulates innate antiviral immune responses targeting Hepatitis C virus infection of hepatocytes', Cell Reports, vol. 17, no. 5, pp. 1357-1368. https://doi.org/10.1016/j.celrep.2016.09.084

TY - JOUR

T1 - Solute carrier NTCP regulates innate antiviral immune responses targeting Hepatitis C virus infection of hepatocytes

AU - Verrier, Eloi R

AU - Colpitts, Che C

AU - Bach, Charlotte

AU - Heydmann, Laura

AU - Zona, Laetitia

AU - Xiao, Fei

AU - Thumann, Christine

AU - Crouchet, Emilie

AU - Gaudin, Raphaël

AU - Sureau, Camille

AU - Cosset, François-Loïc

AU - McKeating, Jane A

AU - Pessaux, Patrick

AU - Hoshida, Yujin

AU - Schuster, Catherine

AU - Zeisel, Mirjam B

AU - Baumert, Thomas F

PY - 2016/10/25

Y1 - 2016/10/25

N2 - 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.

AB - 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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DO - 10.1016/j.celrep.2016.09.084

M3 - Article

C2 - 27783949

SN - 2211-1247

VL - 17

SP - 1357

EP - 1368

JO - Cell Reports

JF - Cell Reports

IS - 5

ER -

Solute carrier NTCP regulates innate antiviral immune responses targeting Hepatitis C virus infection of hepatocytes

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