NatureSep 24, 2025

LRP8 protein helps tick-borne encephalitis virus enter cells

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

LRP8 was identified as a receptor that helps tick-borne encephalitis virus enter cells and as a possible decoy target.

Evidence

This was a preclinical receptor-discovery study using a genome-scale CRISPR-Cas9 screen, human and neuronal cell infection assays, direct binding tests, and lethal TBEV mouse challenge.

Caveat

The therapeutic evidence is preclinical, so human disease relevance and clinical antiviral efficacy are untested.

Simplified

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. 1,2