TBEウイルスが脳細胞へ侵入する仕組みを解明(How the TBE virus enters brain cells)

2025-09-25 カロリンスカ研究所(KI)

<関連情報>

• https://news.ki.se/key-protein-for-tick-borne-infection-revealed-how-the-tbe-virus-enters-brain-cells
• https://www.nature.com/articles/s41586-025-09500-2

LRP8はダニ媒介性脳炎ウイルスの受容体である LRP8 is a receptor for tick-borne encephalitis virus

Eva Mittler,Alexandra L. Tse,Pham-Tue-Hung Tran,Catalina Florez,Javier Janer,Renata Varnaite,Ezgi Kasikci,Vasantha Kumar MV,Michaela Loomis,Wanda Christ,Erik Cazares,Russell R. Bakken,Caroline K. Martin,Xiankun Zeng,Jo Lynne Raymond,Mansoureh Shahsavani,Sara Khanal,Eric R. Wilkinson,Rischa Maya Oktavia,Megan M. Slough,Denise Haslwanter,Julianna Han,Jacob Berrigan,Ebba Rosendal,… Sara Gredmark-Russ
Nature  Published:24 September 2025
DOI:https://doi.org/10.1038/s41586-025-09500-2

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 neuroinflammation^1,2. 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.