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.

气候变化和人口密度加速了高致病性病毒向人类的传播，包括克里米亚-刚果出血热病毒（CCHFV）。在这里，我们报道低密度脂蛋白受体（LDLR）是CCHFV进入细胞的关键受体，在细胞培养物和血管类器官中的CCHFV感染中发挥着至关重要的作用。 CCHFV 和 LDLR 之间的相互作用具有高度特异性，LDLR 蛋白家族的其他成员无法结合或中和病毒。生物传感器实验表明 LDLR 特异性结合 CCHFV 的表面糖蛋白。重要的是，缺乏 LDLR 的小鼠表现出 CCHFV 诱发疾病的延迟。此外，我们还发现 CCHFV 颗粒上存在载脂蛋白 E (ApoE)。我们的研究结果强调了当病毒在蜱细胞中产生时，LDLR 在 CCHFV 感染中的重要作用，无论 ApoE 是否存在。这一发现对于未来针对 CCHFV 疗法的开发具有深远的意义。