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

Research output: Contribution to journal › Article › peer-review

37 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 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
State	Published - 25 Oct 2016

Keywords

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

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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{5963f6f136aa4646b5295fc57fe6a9f7,

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.",

keywords = "NTCP, antiviral therapy, hepatitis B virus, hepatitis C virus, hepatitis D virus, host factor, innate immune responses, signaling, solute carrier, viral entry",

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 Cosset, {Fran{\c c}ois Lo{\"i}c} and McKeating, {Jane A.} and Patrick Pessaux and Yujin Hoshida and Catherine Schuster and Zeisel, {Mirjam B.} and Baumert, {Thomas F.}",

note = "Publisher Copyright: {\textcopyright} 2016 The Author(s)",

year = "2016",

month = oct,

day = "25",

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

language = "English",

volume = "17",

pages = "1357--1368",

journal = "Cell Reports",

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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, FL, 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.

KW - NTCP

KW - antiviral therapy

KW - hepatitis B virus

KW - hepatitis C virus

KW - hepatitis D virus

KW - host factor

KW - innate immune responses

KW - signaling

KW - solute carrier

KW - viral entry

UR - http://www.scopus.com/inward/record.url?scp=84994731753&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2016.09.084

DO - 10.1016/j.celrep.2016.09.084

M3 - Article

C2 - 27783949

AN - SCOPUS:84994731753

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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Keywords

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