AI Summary
fever caused by the Crimean-Congo haemorrhagic fever virus (CCHFV). The virus uses the Low Density Lipoprotein Receptor (LDLR) to bind and enter host cells, leading to infection. The interaction between CCHFV and LDLR is specific, and mice lacking LDLR show a delay in disease progression when infected with CCHFV. This discovery has significant implications for the development of future therapies against CCHFV.
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.
Crimean–Congo haemorrhagic fever virus (CCHFV), the causative agent of Crimean–Congo haemorrhagic fever (CCHF), is an emerging infectious agent that can lead to severe disease and has a mortality of up to 40% (World Health organization). Currently, there are no preventive or effective therapeutic measures available against CCHFV, which is listed as a key priority in the WHO’s R&D Blueprint list of infectious agents with epidemic or pandemic potential. CCHF is a widespread haemorrhagic