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- Title
The low-density lipoprotein receptor and apolipoprotein E associated with CCHFV particles mediate CCHFV entry into cells.
- Authors
Ritter, Maureen; Canus, Lola; Gautam, Anupriya; Vallet, Thomas; Zhong, Li; Lalande, Alexandre; Boson, Bertrand; Gandhi, Apoorv; Bodoirat, Sergueï; Burlaud-Gaillard, Julien; Freitas, Natalia; Roingeard, Philippe; Barr, John N.; Lotteau, Vincent; Legros, Vincent; Mathieu, Cyrille; Cosset, François-Loïc; Denolly, Solène
- 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. This study shows that Crimean-Congo hemorrhagic fever virus (CCHFV) recruits apoE, an exchangeable apolipoprotein that mediates LDL/LDL-R interaction, to promote virion entry via the LDLR. Molecules that down-regulate LDL-R inhibit CCHFV infection.
- Subjects
CONGO (Democratic Republic); LIPOPROTEIN receptors; APOLIPOPROTEIN E; HEMORRHAGIC fever; HEMORRHAGIC diseases; RECEPTOR antibodies; GENE silencing; RABBIT diseases; VIRAL tropism
- Publication
Nature Communications, 2024, Vol 15, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-024-48989-5