RESEARCHERS have identified LRP8, a brain-expressed cell surface protein, as a critical receptor for tick-borne encephalitis virus, offering new insights into viral entry and potential antiviral strategies.
LRP8 acts as the gateway for viral infection
Tick-borne encephalitis virus causes severe neurological disease following tick bites, with increasing incidence across Europe and Asia. While vaccines exist, no targeted therapies are currently available for infected individuals. Using a genome-wide CRISPR–Cas9 screen, scientists at Karolinska Institutet in Stockholm, Sweden, and international collaborators, identified LRP8 as essential for viral infection. Cells lacking LRP8 showed marked resistance to viral entry, whereas overexpression of LRP8 enhanced infection. The viral E glycoprotein binds directly to LRP8, facilitating viral attachment and internalisation, particularly in neuronal cells, revealing a critical step in neuropathogenesis.
Blocking the tick-borne encephalitis virus receptor protects cells and mice
The team developed an LRP8-based soluble decoy that prevented infection in human cell lines and neuronal cultures. In animal models, this decoy offered protection against lethal viral challenge, highlighting LRP8 as a promising target for therapeutic intervention. Understanding how the virus exploits this receptor could guide development of antiviral drugs capable of limiting infection and protecting the central nervous system.
Implications for flavivirus treatment and prevention
This discovery represents the first identification of a single essential host protein acting as a receptor for a flavivirus, a family that includes West Nile virus, yellow fever virus, Japanese encephalitis virus, Zika virus, and dengue virus. Beyond tick-borne encephalitis virus, the findings could accelerate research into host-targeted therapies for related neurotropic viruses. Researchers emphasise that further studies are needed to clarify LRP8’s role in neuronal infection and to translate these insights into clinical treatments.
By pinpointing the tick-borne encephalitis virus receptor, scientists have opened a new avenue for antiviral development, potentially transforming the approach to preventing and treating flavivirus infections.
Reference
Mittler E et al. LRP8 is a receptor for tick-borne encephalitis virus. Nature. 2025; DOI: 10.1038/s41586-025-09500-2.
