Liver-expressed Cd302 and Cr1l limit hepatitis C virus cross-species transmission to mice

Richard J.P. Brown; Birthe Tegtmeyer; Julie Sheldon; Tanvi Khera; Anggakusuma; Daniel Todt; Gabrielle Vieyres; Romy Weller; Sebastian Joecks; Yudi Zhang; Svenja Sake; Dorothea Bankwitz; Kathrin Welsch; Corinne Ginkel; Michael Engelmann; Gisa Gerold; Eike Steinmann; Qinggong Yuan; Michael Ott; Florian W.R. Vondran; Thomas Krey; Luisa J. Ströh; Csaba Miskey; Zoltán Ivics; Vanessa Herder; Wolfgang Baumgärtner; Chris Lauber; Michael Seifert; Alexander W. Tarr; C. Patrick McClure; Glenn Randall; Yasmine Baktash; Alexander Ploss; Viet Loan Dao Thi; Eleftherios Michailidis; Mohsan Saeed; Lieven Verhoye; Philip Meuleman; Natascha Goedecke; Dagmar Wirth; Charles M. Rice; Thomas Pietschmann

doi:10.1126/SCIADV.ABD3233

Liver-expressed Cd302 and Cr1l limit hepatitis C virus cross-species transmission to mice

Richard J.P. Brown, Birthe Tegtmeyer, Julie Sheldon, Tanvi Khera, Anggakusuma, Daniel Todt, Gabrielle Vieyres, Romy Weller, Sebastian Joecks, Yudi Zhang, Svenja Sake, Dorothea Bankwitz, Kathrin Welsch, Corinne Ginkel, Michael Engelmann, Gisa Gerold, Eike Steinmann, Qinggong Yuan, Michael Ott, Florian W.R. VondranThomas Krey, Luisa J. Ströh, Csaba Miskey, Zoltán Ivics, Vanessa Herder, Wolfgang Baumgärtner, Chris Lauber, Michael Seifert, Alexander W. Tarr, C. Patrick McClure, Glenn Randall, Yasmine Baktash, Alexander Ploss, Viet Loan Dao Thi, Eleftherios Michailidis, Mohsan Saeed, Lieven Verhoye, Philip Meuleman, Natascha Goedecke, Dagmar Wirth, Charles M. Rice, Thomas Pietschmann

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

21 Scopus citations

Abstract

Hepatitis C virus (HCV) has no animal reservoir, infecting only humans. To investigate species barrier determinants limiting infection of rodents, murine liver complementary DNA library screening was performed, identifying transmembrane proteins Cd302 and Cr1l as potent restrictors of HCV propagation. Combined ectopic expression in human hepatoma cells impeded HCV uptake and cooperatively mediated transcriptional dysregulation of a noncanonical program of immunity genes. Murine hepatocyte expression of both factors was constitutive and not interferon inducible, while differences in liver expression and the ability to restrict HCV were observed between the murine orthologs and their human counterparts. Genetic ablation of endogenous Cd302 expression in human HCV entry factor transgenic mice increased hepatocyte permissiveness for an adapted HCV strain and dysregulated expression of metabolic process and host defense genes. These findings highlight human-mouse differences in liver-intrinsic antiviral immunity and facilitate the development of next-generation murine models for preclinical testing of HCV vaccine candidates.

Original language	English (US)
Article number	eabd3233
Journal	Science Advances
Volume	6
Issue number	45
DOIs	https://doi.org/10.1126/SCIADV.ABD3233
State	Published - Nov 4 2020

All Science Journal Classification (ASJC) codes

General

Access to Document

10.1126/SCIADV.ABD3233

Cite this

Brown, R. J. P., Tegtmeyer, B., Sheldon, J., Khera, T., Anggakusuma, Todt, D., Vieyres, G., Weller, R., Joecks, S., Zhang, Y., Sake, S., Bankwitz, D., Welsch, K., Ginkel, C., Engelmann, M., Gerold, G., Steinmann, E., Yuan, Q., Ott, M., ... Pietschmann, T. (2020). Liver-expressed Cd302 and Cr1l limit hepatitis C virus cross-species transmission to mice. Science Advances, 6(45), Article eabd3233. https://doi.org/10.1126/SCIADV.ABD3233

@article{9e84622e88a747e7b9a0f5d543699679,

title = "Liver-expressed Cd302 and Cr1l limit hepatitis C virus cross-species transmission to mice",

abstract = "Hepatitis C virus (HCV) has no animal reservoir, infecting only humans. To investigate species barrier determinants limiting infection of rodents, murine liver complementary DNA library screening was performed, identifying transmembrane proteins Cd302 and Cr1l as potent restrictors of HCV propagation. Combined ectopic expression in human hepatoma cells impeded HCV uptake and cooperatively mediated transcriptional dysregulation of a noncanonical program of immunity genes. Murine hepatocyte expression of both factors was constitutive and not interferon inducible, while differences in liver expression and the ability to restrict HCV were observed between the murine orthologs and their human counterparts. Genetic ablation of endogenous Cd302 expression in human HCV entry factor transgenic mice increased hepatocyte permissiveness for an adapted HCV strain and dysregulated expression of metabolic process and host defense genes. These findings highlight human-mouse differences in liver-intrinsic antiviral immunity and facilitate the development of next-generation murine models for preclinical testing of HCV vaccine candidates.",

author = "Brown, {Richard J.P.} and Birthe Tegtmeyer and Julie Sheldon and Tanvi Khera and Anggakusuma and Daniel Todt and Gabrielle Vieyres and Romy Weller and Sebastian Joecks and Yudi Zhang and Svenja Sake and Dorothea Bankwitz and Kathrin Welsch and Corinne Ginkel and Michael Engelmann and Gisa Gerold and Eike Steinmann and Qinggong Yuan and Michael Ott and Vondran, {Florian W.R.} and Thomas Krey and Str{\"o}h, {Luisa J.} and Csaba Miskey and Zolt{\'a}n Ivics and Vanessa Herder and Wolfgang Baumg{\"a}rtner and Chris Lauber and Michael Seifert and Tarr, {Alexander W.} and {Patrick McClure}, C. and Glenn Randall and Yasmine Baktash and Alexander Ploss and Thi, {Viet Loan Dao} and Eleftherios Michailidis and Mohsan Saeed and Lieven Verhoye and Philip Meuleman and Natascha Goedecke and Dagmar Wirth and Rice, {Charles M.} and Thomas Pietschmann",

note = "Publisher Copyright: Copyright {\textcopyright} 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).",

year = "2020",

month = nov,

day = "4",

doi = "10.1126/SCIADV.ABD3233",

language = "English (US)",

volume = "6",

journal = "Science Advances",

issn = "2375-2548",

publisher = "American Association for the Advancement of Science",

number = "45",

}

Brown, RJP, Tegtmeyer, B, Sheldon, J, Khera, T, Anggakusuma, Todt, D, Vieyres, G, Weller, R, Joecks, S, Zhang, Y, Sake, S, Bankwitz, D, Welsch, K, Ginkel, C, Engelmann, M, Gerold, G, Steinmann, E, Yuan, Q, Ott, M, Vondran, FWR, Krey, T, Ströh, LJ, Miskey, C, Ivics, Z, Herder, V, Baumgärtner, W, Lauber, C, Seifert, M, Tarr, AW, Patrick McClure, C, Randall, G, Baktash, Y, Ploss, A, Thi, VLD, Michailidis, E, Saeed, M, Verhoye, L, Meuleman, P, Goedecke, N, Wirth, D, Rice, CM & Pietschmann, T 2020, 'Liver-expressed Cd302 and Cr1l limit hepatitis C virus cross-species transmission to mice', Science Advances, vol. 6, no. 45, eabd3233. https://doi.org/10.1126/SCIADV.ABD3233

TY - JOUR

T1 - Liver-expressed Cd302 and Cr1l limit hepatitis C virus cross-species transmission to mice

AU - Brown, Richard J.P.

AU - Tegtmeyer, Birthe

AU - Sheldon, Julie

AU - Khera, Tanvi

AU - Anggakusuma,

AU - Todt, Daniel

AU - Vieyres, Gabrielle

AU - Weller, Romy

AU - Joecks, Sebastian

AU - Zhang, Yudi

AU - Sake, Svenja

AU - Bankwitz, Dorothea

AU - Welsch, Kathrin

AU - Ginkel, Corinne

AU - Engelmann, Michael

AU - Gerold, Gisa

AU - Steinmann, Eike

AU - Yuan, Qinggong

AU - Ott, Michael

AU - Vondran, Florian W.R.

AU - Krey, Thomas

AU - Ströh, Luisa J.

AU - Miskey, Csaba

AU - Ivics, Zoltán

AU - Herder, Vanessa

AU - Baumgärtner, Wolfgang

AU - Lauber, Chris

AU - Seifert, Michael

AU - Tarr, Alexander W.

AU - Patrick McClure, C.

AU - Randall, Glenn

AU - Baktash, Yasmine

AU - Ploss, Alexander

AU - Thi, Viet Loan Dao

AU - Michailidis, Eleftherios

AU - Saeed, Mohsan

AU - Verhoye, Lieven

AU - Meuleman, Philip

AU - Goedecke, Natascha

AU - Wirth, Dagmar

AU - Rice, Charles M.

AU - Pietschmann, Thomas

N1 - Publisher Copyright: Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

PY - 2020/11/4

Y1 - 2020/11/4

N2 - Hepatitis C virus (HCV) has no animal reservoir, infecting only humans. To investigate species barrier determinants limiting infection of rodents, murine liver complementary DNA library screening was performed, identifying transmembrane proteins Cd302 and Cr1l as potent restrictors of HCV propagation. Combined ectopic expression in human hepatoma cells impeded HCV uptake and cooperatively mediated transcriptional dysregulation of a noncanonical program of immunity genes. Murine hepatocyte expression of both factors was constitutive and not interferon inducible, while differences in liver expression and the ability to restrict HCV were observed between the murine orthologs and their human counterparts. Genetic ablation of endogenous Cd302 expression in human HCV entry factor transgenic mice increased hepatocyte permissiveness for an adapted HCV strain and dysregulated expression of metabolic process and host defense genes. These findings highlight human-mouse differences in liver-intrinsic antiviral immunity and facilitate the development of next-generation murine models for preclinical testing of HCV vaccine candidates.

AB - Hepatitis C virus (HCV) has no animal reservoir, infecting only humans. To investigate species barrier determinants limiting infection of rodents, murine liver complementary DNA library screening was performed, identifying transmembrane proteins Cd302 and Cr1l as potent restrictors of HCV propagation. Combined ectopic expression in human hepatoma cells impeded HCV uptake and cooperatively mediated transcriptional dysregulation of a noncanonical program of immunity genes. Murine hepatocyte expression of both factors was constitutive and not interferon inducible, while differences in liver expression and the ability to restrict HCV were observed between the murine orthologs and their human counterparts. Genetic ablation of endogenous Cd302 expression in human HCV entry factor transgenic mice increased hepatocyte permissiveness for an adapted HCV strain and dysregulated expression of metabolic process and host defense genes. These findings highlight human-mouse differences in liver-intrinsic antiviral immunity and facilitate the development of next-generation murine models for preclinical testing of HCV vaccine candidates.

UR - http://www.scopus.com/inward/record.url?scp=85095676474&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85095676474&partnerID=8YFLogxK

U2 - 10.1126/SCIADV.ABD3233

DO - 10.1126/SCIADV.ABD3233

M3 - Article

C2 - 33148654

AN - SCOPUS:85095676474

SN - 2375-2548

VL - 6

JO - Science Advances

JF - Science Advances

IS - 45

M1 - eabd3233

ER -

Liver-expressed Cd302 and Cr1l limit hepatitis C virus cross-species transmission to mice

Abstract

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this