Understanding tick immunity may be key to preventing killer viruses from spreading

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2 days ago

A tiny tick crawls across your skin, potentially carrying a virus so lethal it kills up to four out of every ten people it infects. Yet that same tick shows no signs of illness whatsoever – it feeds, moves and reproduces as if nothing is wrong.
Scientists studying severe fever with thrombocytopenia syndrome virus (SFTSV) have long wondered why this happens. The pathogen, first identified in China in 2009, causes high fevers, bleeding and organ failure in humans, but leaves ticks completely unharmed.
Alongside colleagues, I conducted research into how ticks can carry deadly viruses without becoming ill themselves. Understanding these resistance mechanisms could help scientists develop new ways to block or weaken tick-borne diseases before they spill over into humans or animals.
The findings come as climate change pushes ticks into new territories around the world. The Asian longhorned tick that carries SFTSV has been identified in Australia, New Zealand and the eastern US, raising concerns the disease could spread to regions that have never seen it before.
Unlike mice, humans or even mosquitoes, ticks pose a unique scientific challenge: most of the molecular tools researchers use to study infection simply don't work in ticks.
Instead, we turned to data analysis. We captured detailed molecular snapshots of infected tick cells, tracking thousands of genes and more than 17,000 proteins simultaneously. This allowed the team to study the cellular response comprehensively, at different time post-infection.
We found that while human cells respond to viral invasion by mounting aggressive immune responses, mobilising multiple defence systems to fight the infection, tick cells take a fundamentally different approach.
Survival strategy
Ticks do have immune systems but they operate very differently from ours. Like humans, ticks have cellular signalling pathways that help detect and respond to infection. Known as Toll, IMD and JAK-STAT, these pathways coordinate defensive responses and trigger the production of antimicrobial proteins.
But when infected with SFTSV, the tick's immune system showed only minimal activity. Instead of launching full-scale defensive responses, these pathways remained largely quiet. The virus appears to have evolved ways to avoid triggering the tick's immune alarm bells.
Instead, the tick cells made major changes to their stress response systems, their production of RNA and proteins, and the pathways that control cell death. (RNA is a molecule that carries genetic instructions – like a working copy of DNA – used by cells to make proteins.) Rather than attacking the virus head-on, tick cells seem to tolerate the infection, reorganising their internal machinery to manage the damage while continuing to function.
This approach makes evolutionary sense when you consider the constraints these tiny creatures face. Mounting a full-blown immune response is energetically expensive – it requires lots of resources and can harm the host's own tissues.
For ticks, which feed only a few times in their life and live off limited energy reserves, a gentler response may be more sustainable. And because this virus has likely been infecting ticks for millions of years, the two have had time to adapt to each other.
Rather than killing the host, the virus may have evolved to fly under the radar, while the tick evolved ways to tolerate it – allowing both to survive and reproduce.
Unexpected antiviral guardians
We identified two key proteins that act as molecular RNA quality controllers. These proteins, called UPF1 and DHX9, are ancient guardians found in all complex life forms, from plants to humans. One of their normal functions involves monitoring and controlling the quality of RNA, the molecular messenger that carries genetic instructions around cells. Think of them as cellular proofreaders, constantly checking that genetic messages are accurate and functional.
My research team first identified these proteins when they appeared as cellular partners that directly interact with viral proteins inside infected cells. This discovery intrigued us because UPF1 and DHX9 were unexpected candidates – they aren't typically associated with antiviral defence – yet they seemed perfectly positioned to detect or process viral RNA, likely because these proteins normally scan RNA for errors, making them well-suited to spot the unusual structures often found in viral genetic material.
To test whether these proteins fight the virus, we used genetic techniques to silence the expression of UPF1 and DHX9 in tick cells, essentially removing these molecular guardians. We found that SFTSV viral growth increased significantly when these proteins were absent, demonstrating their antiviral function.
This suggests that ticks may have evolved a different kind of immune defence known as non-canonical immunity. Instead of attacking viruses head-on using traditional immune systems, ticks seem to use more subtle strategies. In this case, their RNA quality-control proteins act as internal monitors. Because viral RNA often looks different from normal cellular RNA, these proteins may recognise it as unusual. Once detected, they can trigger internal control systems that slow down or block the virus from multiplying – helping the tick stay healthy without a full-blown immune response.
Our research has important implications because UPF1 and DHX9 proteins exist in human cells too. Understanding how they work in ticks could reveal new ways to strengthen human antiviral defences or develop treatments that enhance these natural quality-control mechanisms.
The research also opens possibilities for using these tolerance mechanisms to stop disease – either by strengthening similar defences in humans and animals, or by targeting them in ticks to break the chain of transmission. Future strategies might involve boosting antiviral proteins in wild tick populations or developing treatments that specifically target virus-tick interactions.
Traditional approaches to disease control are struggling to keep up, especially as climate change helps ticks expand into new regions. To prevent future outbreaks, we need a deeper understanding of how ticks, and the viruses they carry, interact with both humans and animals.
Learning how these tiny creatures tolerate deadly pathogens could be key to developing new tools that make people and animals less vulnerable to these diseases – or prevent ticks from passing them on in the first place.
This article is republished from The Conversation under a Creative Commons license. Read the original article.
Marine J. Petit receives funding from European Union's Horizon 2020 Research and Innovation Program under the Marie Skłodowska-Curie grant agreement No 890970.