美国陆军传染病医学研究所Sara Gredmark-Russ课题组报道了LRP8是蜱传脑炎病毒的受体。这一研究成果发表在2025年9月24日出版的国际学术期刊《自然》上。

在这里，小组以基因组规模的CRISPR–Cas9为基础，筛选了LRP8，一种在大脑中高表达的载脂蛋白E和reelin受体，作为TBEV受体。LRP8的下调降低了人细胞的TBEV感染，而其过表达则增强了感染。LRP8直接结合到TBEV E糖蛋白上，介导病毒附着和内化进入细胞。一种基于LRP8的可溶性诱饵可以阻断人类细胞系和神经细胞的感染，并保护小鼠免受致命的TBEV攻击。LRP8作为TBEV受体的作用对TBEV神经发病机制和抗病毒对策的发展具有重要意义。

据悉，蜱传脑炎病毒（TBEV）蜱传脑炎（TBE）是一种严重的、有时危及生命的疾病，其特征是病毒侵入中枢神经系统，并伴有神经炎症症状。与其他正黄病毒主题一样，节肢动物传播的RNA病毒主题，TBEV进入所需的宿主因子仍然不明确。

附：英文原文

Title: LRP8 is a receptor for tick-borne encephalitis virus

Author: Mittler, Eva, Tse, Alexandra L., Tran, Pham-Tue-Hung, Florez, Catalina, Janer, Javier, Varnaite, Renata, Kasikci, Ezgi, MV, Vasantha Kumar, Loomis, Michaela, Christ, Wanda, Cazares, Erik, Bakken, Russell R., Martin, Caroline K., Zeng, Xiankun, Raymond, Jo Lynne, Shahsavani, Mansoureh, Khanal, Sara, Wilkinson, Eric R., Oktavia, Rischa Maya, Slough, Megan M., Haslwanter, Denise, Han, Julianna, Berrigan, Jacob, Rosendal, Ebba, Kielian, Margaret, Manicassamy, Balaji, verby, Anna K., Falk, Anna, Barba-Spaeth, Giovanna, Rey, Felix A., Klingstrm, Jonas, Gavathiotis, Evripidis, Herbert, Andrew S., Chandran, Kartik, Gredmark-Russ, Sara

Issue&Volume: 2025-09-24

Abstract: Tick-borne encephalitis virus (TBEV) causes tick-borne encephalitis (TBE), a severe and sometimes life-threatening disease characterized by viral invasion of the central nervous system with symptoms of neuroinflammation1,2. As with other orthoflaviviruses—enveloped, arthropod-borne RNA viruses—host factors required for TBEV entry remain poorly defined. Here we used a genome-scale CRISPR–Cas9-based screen to identify LRP8, an apolipoprotein E and reelin receptor with high expression in the brain, as a TBEV receptor. LRP8 downregulation reduced TBEV infection in human cells, and its overexpression enhanced infection. LRP8 bound directly to the TBEV E glycoprotein and mediated viral attachment and internalization into cells. An LRP8-based soluble decoy blocked infection of human cell lines and neuronal cells and protected mice from lethal TBEV challenge. LRP8’s role as a TBEV receptor has implications for TBEV neuropathogenesis and the development of antiviral countermeasures.

DOI: 10.1038/s41586-025-09500-2

Source: https://www.nature.com/articles/s41586-025-09500-2