The Crimean-Congo hemorrhagic fever virus (CCHFV) is an emerging pathogen of the Orthonairovirus genus that can cause severe and often lethal hemorrhagic diseases in humans. CCHFV has a broad tropism and can infect a variety of species and tissues. Here, by using gene silencing, blocking antibodies or soluble receptor fragments, we identify the low-density lipoprotein receptor (LDL-R) as a CCHFV entry factor. The LDL-R facilitates binding of CCHFV particles but does not allow entry of Hazara virus (HAZV), another member of the genus. In addition, we show that apolipoprotein E (apoE), an exchangeable protein that mediates LDL/LDL-R interaction, is incorporated on CCHFV particles, though not on HAZV particles, and enhances their specific infectivity by promoting an LDL-R dependent entry. Finally, we show that molecules that decrease LDL-R from the surface of target cells could inhibit CCHFV infection. Our study highlights that CCHFV takes advantage of a lipoprotein receptor and recruits its natural ligand to promote entry into cells.

克里米亚-刚果出血热病毒（CCHFV）是正鼻病毒属的一种新病原体，可引起人类严重且往往致命的出血性疾病。 CCHFV具有广泛的趋向性，可以感染多种物种和组织。在这里，通过使用基因沉默、封闭抗体或可溶性受体片段，我们将低密度脂蛋白受体（LDL-R）确定为CCHFV进入因子。 LDL-R 促进 CCHFV 颗粒的结合，但不允许该属的另一个成员哈扎拉病毒 (HAZV) 进入。此外，我们还发现载脂蛋白E（apoE）是一种介导LDL/LDL-R相互作用的可交换蛋白，它被整合到CCHFV颗粒上（尽管不是HAZV颗粒上），并通过促进LDL-R依赖性进入来增强其特异性感染性。最后，我们证明减少靶细胞表面 LDL-R 的分子可以抑制 CCHFV 感染。我们的研究强调，CCHFV 利用脂蛋白受体并招募其天然配体来促进进入细胞。