Why clues in the brain could help combat tick-borne viruses

Research from the School of Molecular and Cellular Biology has revealed how a tick-borne virus manipulates human brain chemistry to survive, offering new hope for diagnosis and treatment.

The study, funded by Wellcome and published this summer in the Journal of Neuroinflammation and featured in the BMJ, found that the tick-borne encephalitis virus (TBEV), a disease transmitted through tick bites or unpasteurised dairy products, alters key molecules in the brain to aid its survival. 

With symptoms similar to flu, TBEV has around 10,000 to 12,000 cases reported per year. While around half of those infected can clear the virus naturally, others may go on to develop symptoms of TBE. In 10-20% of cases it spreads to the brain and spinal cord, and can cause severe brain inflammation (encephalitis), seizures, and long-term neurological complications.  

Image: Dr Niluka Goonawardane

The research team, led by Dr Niluka Goonawardane, a virologist at the Faculty of Biological Sciences, compared the cerebrospinal fluid (liquid surrounding the brain and spinal cord), from patients with both mild and severe forms of the disease.    

Severe cases had significant changes in metabolites – molecules in the brain that control energy production, signalling, and immune response. These changes suggest that the virus reprogrammes the brain's biochemical pathways to help it replicate and survive.  

Dr Goonawardane, lead researcher at the University of Leeds, explained: 

Now we know that these molecules play a vital role in the survival of the virus and development of severe brain inflammation, they hold huge potential to help us fight this virus. 

“We can use them as natural indicators called biomarkers to diagnose TBEV infection, or to predict if someone is going to develop severe disease, or even as targets for future treatments to prevent severe disease.”   

Three key metabolites linked to severe encephalitis 

Of the 32 metabolites the study identified, three were over twice as high in patients with encephalitis: 

• S-Adenosylmethionine (SAM), which is important for cell signalling, gene expression and epigenetic regulation 
• Fructose 1,6-bisphosphate (FBP1), which is involved in the production of glucose (an essential energy source) 
• Phosphoenolpyruvic acid (PEP), which is linked to energy production and brain inflammation 

Using lab-grown nerve cells, the team used drugs to block these metabolites, reducing the virus growth and confirming their role in the TBEV infection.  

A backdrop of climate change  

The findings have important consequences for strategies to tackle global health issues, given that the spread of ticks has accelerated due to climate change.  TBEV, once limited to parts of Europe and Asia, is now endemic in 27 European countries. The virus was detected in ticks in England for the first time in 2019, signaling a potential emerging threat in the UK.  

Experts have warned that continued public education and healthcare training are crucial for early detection and prevention of tick-borne illnesses. Migratory birds can introduce ticks into new environments, while warming climates help them thrive. 

Dr Madeleine Thomson, Head of Climate Impacts & Adaptation at Wellcome, said: 

“Climate change is pushing ticks into new areas across Europe and the UK - bringing dangerous diseases with them. Some projections suggest tick populations could nearly double by 2080, sharply increasing the risk of viruses like TBEV emerging in regions where they’ve never been seen before.  

“This research marks a vital advance. TBEV is among the most serious tick-borne threats in our region, and deepening our understanding is essential for faster diagnosis, better treatment, and stronger public health protection.”  

As TBEV cases continue to rise, this research could pave the way for better understanding, diagnosing and even treatment for one of the most dangerous tick-borne viruses threatening Europe.  

Further information 

Changes in metabolite profiles in the cerebrospinal fluid and in human neuronal cells upon tick-borne encephalitis virus infection was published on 14 June 2025 in the Journal of Neuroinflamation. Authored by Satoshi Suyama, Sally Boxall, Benjamin Grace, Andrea Fořtová, Martina Pychova, Lenka Krbkova, Rupasri Mandal, David Wishart, Diane E. Griffin, Daniel Růžek & Niluka Goonawardane 

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