Overview: Why this discovery matters for TBE treatment
Tick-borne encephalitis (TBE) remains a significant public health concern in Europe and parts of Asia, where colder winters and milder seasons have contributed to a growing presence of ticks and a higher risk of transmission. While vaccination provides solid protection for many, immunization is not universal, and access and cost considerations can limit uptake. In Sweden, health authorities reported 305 TBE cases by August this year, according to Folkhälsomyndigheten. Although 2024’s final tally is likely to be lower than the record 595 cases observed in 2023, the disease burden remains notably higher than a decade ago. Against this backdrop, identifying a potential treatment—beyond prevention—is a crucial objective for clinicians and patients alike.
The latest breakthrough comes from an international research collaboration led by Karolinska Institutet. The team mapped how the TBE virus gains entry into human brain cells and identified a host protein that the virus must interact with to infect cells. This discovery, published in Nature, marks a possible first step toward therapeutic strategies that could limit disease progression after infection.
The discovery: LRP8 as a key virus entry receptor
The researchers focused on a protein known as LRP8, a receptor on the surface of cells that is abundantly expressed in neural tissue. By systematically removing thousands of host genes in cell cultures and exposing them to the TBE virus, they found that cells lacking LRP8 were resistant to infection. In essence, LRP8 appears to act as a doorway the virus uses to bind and gain access to the cell interior. The team demonstrated that the TBE virus binds to LRP8, enabling cellular entry and subsequent infection. This is the first time scientists have pinpointed a single host cell protein that serves as a receptor for a flavivirus-related pathogen, according to the study’s senior author.
How the study was conducted
The project employed high-throughput genetic screening to disable individual genes across thousands of cells. By observing which cells survived viral exposure, the researchers could infer which gene products were essential for infection. The absence of LRP8 protected cells from TBE, indicating the receptor’s pivotal role in the virus’s life cycle. The research team includes researchers from Karolinska Institutet and collaborators across international institutions, and the work has been published in Nature, underscoring the significance of the findings within the broader field of infectious diseases.
What this could mean for patients and future therapies
Identifying LRP8 as a necessary entry point for the TBE virus opens multiple pathways for therapeutic development. In the near term, scientists may explore molecules that block the interaction between the virus and LRP8 or modulate receptor availability to reduce viral entry. Such strategies could potentially lessen viral spread in the brain, reduce the severity of neurological symptoms, and improve outcomes for people who become infected. It is important to note that translating this basic science into an approved treatment will require extensive preclinical testing and clinical trials to assess safety and effectiveness, particularly in diverse patient populations and across different stages of infection.
Context: TBE, flaviviruses, and next steps
TBE belongs to the flavivirus family, which also includes yellow fever, Japanese encephalitis, and dengue. The discovery of a single, essential host protein that enables entry could have implications beyond TBE, potentially guiding research into receptor-targeted therapies for other flavivirus infections. The researchers emphasize that this finding is an important first step, not a finished therapy, and further work is needed to develop practical, safe treatments that can complement vaccination and public health measures.
About TBE prevention and current challenges
Vaccination remains the best line of defense against TBE for many populations. However, practical barriers such as cost, access, and personal choice mean that vaccination alone cannot eliminate risk. As tick habitats expand with changing climates, ongoing surveillance and research into treatments that can mitigate disease progression are essential. The new LRP8 finding represents a promising avenue in the broader effort to reduce the burden of TBE in Europe and Asia.
About the study
The Nature article is led by researchers at Karolinska Institutet with international collaborators. The study’s senior author highlighted that identifying a single host protein essential for a flavivirus receptor is a landmark discovery with potential to inspire new treatment approaches not only for TBE, but for related infections as well.
