Logo image
LRP8 is a receptor for tick-borne encephalitis virus
Journal article   Peer reviewed

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, …
Nature (London), Vol.646(8086), pp.945-952
10/23/2025
DOI: 10.1038/s41586-025-09500-2
PMID: 40993380
url
http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-244874View
Open Access

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 . 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.

Details

Metrics

30 Record Views
Logo image