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The low-density lipoprotein receptor and apolipoprotein E associated with CCHFV particles mediate CCHFV entry into cells

Author

Listed:
  • Maureen Ritter

    (CIRI – Centre International de Recherche en Infectiologie, Univ. Lyon, Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS de Lyon)

  • Lola Canus

    (CIRI – Centre International de Recherche en Infectiologie, Univ. Lyon, Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS de Lyon)

  • Anupriya Gautam

    (CIRI – Centre International de Recherche en Infectiologie, Univ. Lyon, Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS de Lyon)

  • Thomas Vallet

    (CIRI – Centre International de Recherche en Infectiologie, Univ. Lyon, Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS de Lyon)

  • Li Zhong

    (CIRI – Centre International de Recherche en Infectiologie, Univ. Lyon, Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS de Lyon)

  • Alexandre Lalande

    (CIRI – Centre International de Recherche en Infectiologie, Univ. Lyon, Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS de Lyon)

  • Bertrand Boson

    (CIRI – Centre International de Recherche en Infectiologie, Univ. Lyon, Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS de Lyon)

  • Apoorv Gandhi

    (CIRI – Centre International de Recherche en Infectiologie, Univ. Lyon, Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS de Lyon)

  • Sergueï Bodoirat

    (CIRI – Centre International de Recherche en Infectiologie, Univ. Lyon, Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS de Lyon)

  • Julien Burlaud-Gaillard

    (Université de Tours and CHRU de Tours
    Plateforme IBiSA de Microscopie Electronique)

  • Natalia Freitas

    (CIRI – Centre International de Recherche en Infectiologie, Univ. Lyon, Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS de Lyon)

  • Philippe Roingeard

    (Université de Tours and CHRU de Tours
    Plateforme IBiSA de Microscopie Electronique)

  • John N. Barr

    (University of Leeds)

  • Vincent Lotteau

    (Inserm)

  • Vincent Legros

    (CIRI – Centre International de Recherche en Infectiologie, Univ. Lyon, Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS de Lyon
    Université de Lyon)

  • Cyrille Mathieu

    (CIRI – Centre International de Recherche en Infectiologie, Univ. Lyon, Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS de Lyon)

  • François-Loïc Cosset

    (CIRI – Centre International de Recherche en Infectiologie, Univ. Lyon, Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS de Lyon)

  • Solène Denolly

    (CIRI – Centre International de Recherche en Infectiologie, Univ. Lyon, Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS de Lyon)

Abstract

The Crimean-Congo hemorrhagic fever virus (CCHFV) is an emerging pathogen of the Orthonairovirus genus that can cause severe and often lethal hemorrhagic diseases in humans. CCHFV has a broad tropism and can infect a variety of species and tissues. Here, by using gene silencing, blocking antibodies or soluble receptor fragments, we identify the low-density lipoprotein receptor (LDL-R) as a CCHFV entry factor. The LDL-R facilitates binding of CCHFV particles but does not allow entry of Hazara virus (HAZV), another member of the genus. In addition, we show that apolipoprotein E (apoE), an exchangeable protein that mediates LDL/LDL-R interaction, is incorporated on CCHFV particles, though not on HAZV particles, and enhances their specific infectivity by promoting an LDL-R dependent entry. Finally, we show that molecules that decrease LDL-R from the surface of target cells could inhibit CCHFV infection. Our study highlights that CCHFV takes advantage of a lipoprotein receptor and recruits its natural ligand to promote entry into cells.

Suggested Citation

  • Maureen Ritter & Lola Canus & Anupriya Gautam & Thomas Vallet & Li Zhong & Alexandre Lalande & Bertrand Boson & Apoorv Gandhi & Sergueï Bodoirat & Julien Burlaud-Gaillard & Natalia Freitas & Philippe , 2024. "The low-density lipoprotein receptor and apolipoprotein E associated with CCHFV particles mediate CCHFV entry into cells," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48989-5
    DOI: 10.1038/s41467-024-48989-5
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    References listed on IDEAS

    as
    1. Jovan Nikolic & Laura Belot & Hélène Raux & Pierre Legrand & Yves Gaudin & Aurélie Albertini, 2018. "Structural basis for the recognition of LDL-receptor family members by VSV glycoprotein," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    2. Lars E. Clark & Sarah A. Clark & ChieYu Lin & Jianying Liu & Adrian Coscia & Katherine G. Nabel & Pan Yang & Dylan V. Neel & Hyo Lee & Vesna Brusic & Iryna Stryapunina & Kenneth S. Plante & Asim A. Ah, 2022. "VLDLR and ApoER2 are receptors for multiple alphaviruses," Nature, Nature, vol. 602(7897), pages 475-480, February.
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