Hepatitis C virus infects and perturbs liver stem cells

Nathan L. Meyers; Tal Ashuach; Danielle E. Lyons; Mir M. Khalid; Camille R. Simoneau; Ann L. Erickson; Mehdi Bouhaddou; Thong T. Nguyen; G. Renuka Kumar; Taha Y. Taha; Vaishaali Natarajan; Jody L. Baron; Norma Neff; Fabio Zanini; Tokameh Mahmoudi; Stephen R. Quake; Nevan J. Krogan; Stewart Cooper; Todd C. McDevitt; Nir Yosef; Melanie Ott

doi:10.1128/mbio.01318-23

Hepatitis C virus infects and perturbs liver stem cells

Nathan L. Meyers, Tal Ashuach, Danielle E. Lyons, Mir M. Khalid, Camille R. Simoneau, Ann L. Erickson, Mehdi Bouhaddou, Thong T. Nguyen, G. Renuka Kumar, Taha Y. Taha, Vaishaali Natarajan, Jody L. Baron, Norma Neff, Fabio Zanini, Tokameh Mahmoudi, Stephen R. Quake, Nevan J. Krogan, Stewart Cooper, Todd C. McDevitt, Nir YosefMelanie Ott

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

Abstract

Hepatitis C virus (HCV) is the leading cause of death from liver disease. How HCV infection causes lasting liver damage and increases cancer risk remains unclear. Here, we identify bipotent liver stem cells as novel targets for HCV infection, and their erroneous differentiation as the potential cause of impaired liver regeneration and cancer development. We show 3D organoids generated from liver stem cells from actively HCV-infected individuals carry replicating virus and maintain low-grade infection over months. Organoids can be infected with a primary HCV isolate. Virus-inclusive single-cell RNA sequencing uncovered transcriptional reprogramming in HCV⁺ cells supporting hepatocytic differentiation, cancer stem cell development, and viral replication while stem cell proliferation and interferon signaling are disrupted. Our data add a new pathogenesis mechanism—infection of liver stem cells—to the biology of HCV infection that may explain progressive liver damage and enhanced cancer risk through an altered stem cell state.

Original language	English
Article number	0131823
Journal	mBio
Volume	14
Issue number	6
DOIs	https://doi.org/10.1128/mbio.01318-23
State	Published - Dec 2023
Externally published	Yes

All Science Journal Classification (ASJC) codes

Microbiology
Virology

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Meyers, N. L., Ashuach, T., Lyons, D. E., Khalid, M. M., Simoneau, C. R., Erickson, A. L., Bouhaddou, M., Nguyen, T. T., Renuka Kumar, G., Taha, T. Y., Natarajan, V., Baron, J. L., Neff, N., Zanini, F., Mahmoudi, T., Quake, S. R., Krogan, N. J., Cooper, S., McDevitt, T. C., ... Ott, M. (2023). Hepatitis C virus infects and perturbs liver stem cells. mBio, 14(6), Article 0131823. https://doi.org/10.1128/mbio.01318-23

@article{04bf4eab0fb94bd0b498151b54f907ed,

title = "Hepatitis C virus infects and perturbs liver stem cells",

abstract = "Hepatitis C virus (HCV) is the leading cause of death from liver disease. How HCV infection causes lasting liver damage and increases cancer risk remains unclear. Here, we identify bipotent liver stem cells as novel targets for HCV infection, and their erroneous differentiation as the potential cause of impaired liver regeneration and cancer development. We show 3D organoids generated from liver stem cells from actively HCV-infected individuals carry replicating virus and maintain low-grade infection over months. Organoids can be infected with a primary HCV isolate. Virus-inclusive single-cell RNA sequencing uncovered transcriptional reprogramming in HCV+ cells supporting hepatocytic differentiation, cancer stem cell development, and viral replication while stem cell proliferation and interferon signaling are disrupted. Our data add a new pathogenesis mechanism—infection of liver stem cells—to the biology of HCV infection that may explain progressive liver damage and enhanced cancer risk through an altered stem cell state.",

author = "Meyers, {Nathan L.} and Tal Ashuach and Lyons, {Danielle E.} and Khalid, {Mir M.} and Simoneau, {Camille R.} and Erickson, {Ann L.} and Mehdi Bouhaddou and Nguyen, {Thong T.} and {Renuka Kumar}, G. and Taha, {Taha Y.} and Vaishaali Natarajan and Baron, {Jody L.} and Norma Neff and Fabio Zanini and Tokameh Mahmoudi and Quake, {Stephen R.} and Krogan, {Nevan J.} and Stewart Cooper and McDevitt, {Todd C.} and Nir Yosef and Melanie Ott",

note = "Publisher Copyright: Copyright {\textcopyright} 2023 Meyers et al.",

year = "2023",

month = dec,

doi = "10.1128/mbio.01318-23",

language = "الإنجليزيّة",

volume = "14",

journal = "mBio",

issn = "2161-2129",

publisher = "American Society for Microbiology",

number = "6",

}

Meyers, NL, Ashuach, T, Lyons, DE, Khalid, MM, Simoneau, CR, Erickson, AL, Bouhaddou, M, Nguyen, TT, Renuka Kumar, G, Taha, TY, Natarajan, V, Baron, JL, Neff, N, Zanini, F, Mahmoudi, T, Quake, SR, Krogan, NJ, Cooper, S, McDevitt, TC, Yosef, N & Ott, M 2023, 'Hepatitis C virus infects and perturbs liver stem cells', mBio, vol. 14, no. 6, 0131823. https://doi.org/10.1128/mbio.01318-23

TY - JOUR

T1 - Hepatitis C virus infects and perturbs liver stem cells

AU - Meyers, Nathan L.

AU - Ashuach, Tal

AU - Lyons, Danielle E.

AU - Khalid, Mir M.

AU - Simoneau, Camille R.

AU - Erickson, Ann L.

AU - Bouhaddou, Mehdi

AU - Nguyen, Thong T.

AU - Renuka Kumar, G.

AU - Taha, Taha Y.

AU - Natarajan, Vaishaali

AU - Baron, Jody L.

AU - Neff, Norma

AU - Zanini, Fabio

AU - Mahmoudi, Tokameh

AU - Quake, Stephen R.

AU - Krogan, Nevan J.

AU - Cooper, Stewart

AU - McDevitt, Todd C.

AU - Yosef, Nir

AU - Ott, Melanie

PY - 2023/12

Y1 - 2023/12

N2 - Hepatitis C virus (HCV) is the leading cause of death from liver disease. How HCV infection causes lasting liver damage and increases cancer risk remains unclear. Here, we identify bipotent liver stem cells as novel targets for HCV infection, and their erroneous differentiation as the potential cause of impaired liver regeneration and cancer development. We show 3D organoids generated from liver stem cells from actively HCV-infected individuals carry replicating virus and maintain low-grade infection over months. Organoids can be infected with a primary HCV isolate. Virus-inclusive single-cell RNA sequencing uncovered transcriptional reprogramming in HCV+ cells supporting hepatocytic differentiation, cancer stem cell development, and viral replication while stem cell proliferation and interferon signaling are disrupted. Our data add a new pathogenesis mechanism—infection of liver stem cells—to the biology of HCV infection that may explain progressive liver damage and enhanced cancer risk through an altered stem cell state.

AB - Hepatitis C virus (HCV) is the leading cause of death from liver disease. How HCV infection causes lasting liver damage and increases cancer risk remains unclear. Here, we identify bipotent liver stem cells as novel targets for HCV infection, and their erroneous differentiation as the potential cause of impaired liver regeneration and cancer development. We show 3D organoids generated from liver stem cells from actively HCV-infected individuals carry replicating virus and maintain low-grade infection over months. Organoids can be infected with a primary HCV isolate. Virus-inclusive single-cell RNA sequencing uncovered transcriptional reprogramming in HCV+ cells supporting hepatocytic differentiation, cancer stem cell development, and viral replication while stem cell proliferation and interferon signaling are disrupted. Our data add a new pathogenesis mechanism—infection of liver stem cells—to the biology of HCV infection that may explain progressive liver damage and enhanced cancer risk through an altered stem cell state.

UR - http://www.scopus.com/inward/record.url?scp=85184168320&partnerID=8YFLogxK

U2 - 10.1128/mbio.01318-23

DO - 10.1128/mbio.01318-23

M3 - مقالة

C2 - 37938000

SN - 2161-2129

VL - 14

JO - mBio

JF - mBio

IS - 6

M1 - 0131823

ER -

Hepatitis C virus infects and perturbs liver stem cells

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All Science Journal Classification (ASJC) codes

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