Crimean–Congo haemorrhagic fever virus uses LDLR to bind and enter host cells

Climate change and population densities accelerated transmission of highly pathogenic viruses to humans, including the Crimean–Congo haemorrhagic fever virus (CCHFV). Here we report that the Low Density Lipoprotein Receptor (LDLR) is a critical receptor for CCHFV cell entry, playing a vital role in...

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Published in:	Nature microbiology Vol. 9; no. 6; pp. 1499 - 1512
Main Authors:	Monteil, Vanessa M., Wright, Shane C., Dyczynski, Matheus, Kellner, Max J., Appelberg, Sofia, Platzer, Sebastian W., Ibrahim, Ahmed, Kwon, Hyesoo, Pittarokoilis, Ioannis, Mirandola, Mattia, Michlits, Georg, Devignot, Stephanie, Elder, Elizabeth, Abdurahman, Samir, Bereczky, Sándor, Bagci, Binnur, Youhanna, Sonia, Aastrup, Teodor, Lauschke, Volker M., Salata, Cristiano, Elaldi, Nazif, Weber, Friedemann, Monserrat, Nuria, Hawman, David W., Feldmann, Heinz, Horn, Moritz, Penninger, Josef M., Mirazimi, Ali
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 2024 Nature Publishing Group
Subjects:	13/1 13/31 14/63 631/326/596/2555 631/326/596/2557 64/60 96/10 Animals Apolipoprotein E Apolipoproteins E - genetics Apolipoproteins E - metabolism Biomedical and Life Sciences Biosensors Blood vessels Cell culture Climate change Crimean hemorrhagic fever Fever Glycoproteins Hemorrhagic Fever Virus, Crimean-Congo - genetics Hemorrhagic Fever Virus, Crimean-Congo - physiology Hemorrhagic Fever, Crimean - metabolism Hemorrhagic Fever, Crimean - virology Humans Infections Infectious Diseases LDLR protein Life Sciences Low density lipoprotein Low density lipoprotein receptors Medical Microbiology Medicin och hälsovetenskap Mice Mice, Knockout Microbiology Organoids Parasitology Population density Receptor density Receptors, LDL - genetics Receptors, LDL - metabolism Receptors, Virus - metabolism Ticks - metabolism Ticks - virology Virology Virus Internalization Viruses
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Summary:	Climate change and population densities accelerated transmission of highly pathogenic viruses to humans, including the Crimean–Congo haemorrhagic fever virus (CCHFV). Here we report that the Low Density Lipoprotein Receptor (LDLR) is a critical receptor for CCHFV cell entry, playing a vital role in CCHFV infection in cell culture and blood vessel organoids. The interaction between CCHFV and LDLR is highly specific, with other members of the LDLR protein family failing to bind to or neutralize the virus. Biosensor experiments demonstrate that LDLR specifically binds the surface glycoproteins of CCHFV. Importantly, mice lacking LDLR exhibit a delay in CCHFV-induced disease. Furthermore, we identified the presence of Apolipoprotein E (ApoE) on CCHFV particles. Our findings highlight the essential role of LDLR in CCHFV infection, irrespective of ApoE presence, when the virus is produced in tick cells. This discovery holds profound implications for the development of future therapies against CCHFV. Laboratory and clinical strains of Crimean–Congo haemorrhagic fever virus use LDLR to bind and enter host cells in blood vessel organoids and mice. Infection can also occur through ApoE, possibly present on virus particles.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2058-5276 2058-5276
DOI:	10.1038/s41564-024-01672-3