Key protein for tick-borne infection revealed – how the TBE virus enters brain cells
Researchers at Karolinska Institutet, together with international colleagues, have identified a protein that is crucial for the TBE virus to infect human cells. The discovery, published in the journal Nature, could pave the way for new treatments for tick-borne encephalitis.
Tick-borne encephalitis virus (TBEV) causes tick-borne encephalitis. An international team of researchers has now succeeded in identifying a protein on the surface of cells that the virus uses to enter the body.
The TBE virus is spread through tick bites and can cause serious neurological disease. The virus is common in large parts of Europe and Asia, and the number of cases is increasing as the tick population grows. Although there is a vaccine against TBE, there are no specific treatments for those who have already been infected.
"The TBE virus is a high-risk virus that requires special handling in the laboratory with high standards for protective clothing, equipment and ventilation," says Pham-Tue-Hung Tran, postdoctoral researcher at the Department of Medicine, Karolinska Institutet, and one of the lead authors of the study.
Opens the door for the virus
To understand how the virus infects human cells, a method was used in which a library of thousands of cell variants, with different genes removed in each cell, was exposed to TBEV. The cells that survived lacked a specific gene. This gene contains the code for a protein that proved to be crucial for infection: LRP8.
"LRP8 is a protein on the cell surface that is highly expressed in brain cells," says Sara Gredmark Russ, Associate Professor of Infectious Diseases at the Department of Medicine, Karolinska Institutet, who is responsible for the study at KI.
LRP8 acts as a kind of door opener for the virus. In the study, the researchers show that TBEV's surface protein binds specifically to LRP8, which enables the virus to enter cells – especially nerve cells in the brain.
Useful for other diseases
– We need to conduct more studies to understand exactly how LRP8 contributes to TBEV causing disease. The next step will be to try to understand what happens in the brain's neurons during an infection," says Sara Gredmark Russ.
The discovery opens new opportunities to develop drugs that could prevent the virus from entering the body and limit the infection if someone has been infected.
TBEV is a flavivirus, which are all spread by mosquitoes or ticks and are also responsible for diseases such as yellow fever, Japanese encephalitis and dengue fever.
‘This is the first time anyone has succeeded in identifying a single essential host cell protein that acts as a receptor for flaviviruses, which opens up the possibility of discovering receptors and better treatments for other flavivirus-caused diseases as well,’ says Sara Gredmark Russ.
The study is a collaboration between researchers from Karolinska Institutet, Albert Einstein College of Medicine and the United States Army Medical Institute of Infectious Diseases.
The study is funded by, among others, the Swedish Research Council, the Marianne and Marcus Wallenberg Foundation, and Region Stockholm. See the study for conflicts of interest.
Publication
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, Erik Cazares, Russell R. Bakken, Caroline K. Martin, Xiankun Zeng, Jo Lynne Raymond, Mansoureh Shahsavani, Sara Khanal, Eric R. Wilkinson, Rischa Maya Oktavia, Megan M. Slough, Denise Haslwanter, Julianna Han, Jacob Berrigan, Ebba Rosendal, Margaret Kielian, Balaji Manicassamy, Anna K. Överby, Anna Falk, Giovanna Barba-Spaeth, Felix A. Rey, Jonas Klingström, Evripidis Gavathiotis, Andrew S. Herbert, Kartik Chandran, Sara Gredmark-Russ Nature, online 24 September 2025. doi:10.1038/s41586-025-09500-2.