First steps toward a treatment for tick-borne encephalitis (TBE)
Tick-borne encephalitis (TBE) remains a significant public health challenge in Europe and Asia, where climate-driven changes are expanding the habitats of ticks and the viruses they carry. While vaccines provide strong protection for many, not everyone can or wants to be vaccinated, and a specific treatment for those who become infected has been elusive. In Sweden, health authorities had logged 305 TBE cases by August this year, according to the Public Health Agency of Sweden, with 2023’s record total of 595 cases illustrating how quickly the situation can shift. Against this backdrop, a potential breakthrough offers a glimmer of hope: researchers may have found the first material key to stopping the virus from invading brain cells.
A breakthrough: identifying the virus’s entry route into the brain
A multinational team led by researchers at Karolinska Institutet reports a landmark finding in the journal Nature. They have identified a human cell surface protein, called LRP8, that the TBE virus appears to use to enter cells. LRP8 is a receptor expressed at high levels on neurons, which helps explain why TBE can cause inflammation of the brain.
In a large-scale loss-of-function screen, the researchers revealed that thousands of cells had specific genes knocked out to test whether they could still be infected by the TBE virus. Remarkably, cells lacking the gene responsible for LRP8 formation were notably resistant to infection. This suggested that LRP8 acts as a gatekeeper for the virus, enabling it to attach and gain access to vulnerable cells in the nervous system.
From discovery to potential therapies
The discovery that the TBE virus relies on LRP8 to infect cells provides a plausible target for therapeutic intervention. If researchers can design drugs that block the virus-LRP8 interaction or reduce LRP8 activity in relevant brain tissues, they may limit how quickly the disease progresses after infection. It is important to stress that this is an early, foundational finding rather than an immediate treatment option. Much work remains to translate this mechanism into safe and effective medicines, including preclinical studies and eventual clinical trials.
What this could mean for TBE and other flaviviruses
Flaviviruses, a family that includes dengue, yellow fever, and Japanese encephalitis, share common biology, and identifying a single host protein that acts as a receptor for a flavivirus is a notable advance. The study’s senior author, a professor of infectious diseases at Karolinska Institutet, highlighted that this finding not only opens doors for improving TBE care but could also illuminate strategies against other flavivirus infections. As researchers pursue compounds that disrupt the virus’s use of LRP8, the broader goal is to calm disease severity, protect brain function, and reduce hospitalization and long-term consequences for patients who become infected with TBE.
Next steps and a cautious optimism
Experts emphasize that, while promising, the road to a practical therapy is longer than a single discovery. Future work will investigate how to safely inhibit LRP8 in humans without disrupting its normal cellular roles, determine whether the virus uses LRP8 in all affected tissues, and assess potential side effects. The findings, published in Nature, provide a concrete target for medicinal chemistry campaigns and preclinical testing. If progress continues, this line of research could lead to a new class of antivirals that complement vaccination and public health measures, offering a crucial tool against TBE and potentially other flaviviruses.
Bottom line
The identification of LRP8 as a critical receptor for TBE virus entry marks an important first step toward treatments that could alter the course of infection. While a practical therapy is not yet on the horizon, this discovery lays the groundwork for drug development that might one day reduce the burden of fästingburen hjärninflammation and related diseases.
