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

Maureen Ritter, Lola Canus, Anupriya Gautam, Thomas Vallet, Li Zhong, Alexandre Lalande, Bertrand Boson, Apoorv Gandhi, Sergueï Bodoirat, Julien Burlaud-Gaillard, Natalia Freitas, Philippe Roingeard, John N. Barr, Vincent Lotteau, Vincent Legros, Cyrille Mathieu, François-Loïc Cosset () and Solène Denolly ()
Additional contact information
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
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
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
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

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-48989-5

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