The low-density lipoprotein receptor and apolipoprotein E associated with CCHFV particles mediate CCHFV entry into cells
Infection with Crimean-Congo haemorrhagic fever virus (CCHFV) causes a disease that can lead to haemorrhagic syndrome, with a risk of death of up to 30%. The disease is transmitted by the bite of ticks of the genus Hyalomma.
It is endemic in Africa, Asia, the Middle East and certain countries in Eastern and Southern Europe, including Spain. In France, VFHCC has been detected in ticks taken from farmed cattle, but no human case has yet been detected. However, this infection is a major threat, and it is therefore essential to develop fundamental research projects to discover new knowledge about this pathogen. In particular, the study of the receptor that is the virus's entry point into cells is essential if therapeutic targets are to be identified. We demonstrate that the low-density lipoprotein receptor, or LDL-R, normally used to bring cholesterol into cells, is usurped by CCHFV to allow viral particles to enter.
We also show that CCHFV particles incorporate a component of low-density lipoproteins, apolipoprotein E, which facilitates interaction between the viral particles and the receptor. Finally, we demonstrate that small molecules that prevent the arrival of LDL-R at the cell surface inhibit the infection of cells by CCHFV, opening up new avenues of investigation for the development of treatments.
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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, Solène Denolly.
Nat Commun. 2024 May 28;15(1):4542.doi: 10.1038/s41467-024-48989-5