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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Veröffentlicht in:Nature microbiology Jg. 9; H. 6; S. 1499 - 1512
Hauptverfasser: 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
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 01.06.2024
Nature Publishing Group
Schlagworte:
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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
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
ISSN:2058-5276, 2058-5276
Online-Zugang:Volltext
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Zusammenfassung: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.
Bibliographie:ObjectType-Article-1
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ISSN:2058-5276
2058-5276
DOI:10.1038/s41564-024-01672-3