HMN 2025: How the virus enters brain cells

Researchers at Karolinska Institutet, together with international colleagues, have identified a protein on the surface of cells that is crucial to allowing the tick-borne encephalitis (TBE) virus to enter the body. The discovery, published in the journal Nature, could pave the way for new treatments for TBE.

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.

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 the TBE virus. 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 the TBE virus’s surface protein binds specifically to LRP8, which enables the virus to enter cells—especially nerve cells in the brain.

“We need to conduct more studies to understand exactly how LRP8 contributes to the TBE virus causing disease. The next step will be to try to understand what happens in the brain’s neurons during an infection,” says Russ.

The discovery provides new opportunities to develop drugs that could prevent the virus from entering the body and limit the infection if someone has been infected. The TBE virus 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 Russ.

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