Crimean-Congo haemorrhagic fever virus uses LDLR to bind and enter host cells.
Autor: | Monteil VM; Unit of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden.; Public Health Agency of Sweden, Solna, Sweden., Wright SC; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden., Dyczynski M; Acus Laboratories GmbH, Cologne, Germany.; JLP Health GmbH, Vienna, Austria., Kellner MJ; IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Science, Vienna, Austria.; Vienna Biocenter PhD Program, a Doctoral School of the University of Vienna and the Medical University of Vienna, Vienna, Austria., Appelberg S; Public Health Agency of Sweden, Solna, Sweden., Platzer SW; IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Science, Vienna, Austria.; Vienna Biocenter PhD Program, a Doctoral School of the University of Vienna and the Medical University of Vienna, Vienna, Austria., Ibrahim A; Attana AB, Stockholm, Sweden., Kwon H; National Veterinary Institute, Uppsala, Sweden., Pittarokoilis I; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden., Mirandola M; Department of Molecular Medicine, University of Padova, Padova, Italy., Michlits G; JLP Health GmbH, Vienna, Austria., Devignot S; Unit of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden.; Public Health Agency of Sweden, Solna, Sweden., Elder E; National Veterinary Institute, Uppsala, Sweden., Abdurahman S; Public Health Agency of Sweden, Solna, Sweden., Bereczky S; Public Health Agency of Sweden, Solna, Sweden., Bagci B; Department of Nutrition and Dietetics, Faculty of Health Sciences, Sivas Cumhuriyet University, Sivas, Turkey., Youhanna S; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden., Aastrup T; Attana AB, Stockholm, Sweden., Lauschke VM; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.; University Tübingen, Tübingen, Germany.; Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany., Salata C; Department of Molecular Medicine, University of Padova, Padova, Italy., Elaldi N; Department of Infectious Diseases and Clinical Microbiology, Medical Faculty, Cumhuriyet University, Sivas, Turkey., Weber F; Institute for Virology, FB10-Veterinary Medicine, Justus-Liebig University, Gießen, Germany., Monserrat N; University of Barcelona, Barcelona, Spain.; Pluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.; Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain., Hawman DW; Rocky Mountain Laboratories, NIAID/NIH, Hamilton, MT, USA., Feldmann H; Rocky Mountain Laboratories, NIAID/NIH, Hamilton, MT, USA., Horn M; Acus Laboratories GmbH, Cologne, Germany.; JLP Health GmbH, Vienna, Austria., Penninger JM; IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Science, Vienna, Austria. josef.penninger@helmholtz-hzi.de.; Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria. josef.penninger@helmholtz-hzi.de.; Helmholtz Centre for Infection Research, Braunschweig, Germany. josef.penninger@helmholtz-hzi.de.; Department of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada. josef.penninger@helmholtz-hzi.de., Mirazimi A; Unit of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden. ali.mirazimi@ki.se.; Public Health Agency of Sweden, Solna, Sweden. ali.mirazimi@ki.se.; National Veterinary Institute, Uppsala, Sweden. ali.mirazimi@ki.se. |
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Jazyk: | angličtina |
Zdroj: | Nature microbiology [Nat Microbiol] 2024 Jun; Vol. 9 (6), pp. 1499-1512. Date of Electronic Publication: 2024 Mar 28. |
DOI: | 10.1038/s41564-024-01672-3 |
Abstrakt: | 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. (© 2024. The Author(s).) |
Databáze: | MEDLINE |
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