Researchers uncover unexpected limit to SARS-CoV-2’s immune defenses

A new collaborative study has revealed a hidden weakness in how the COVID-19 virus (SARS-CoV-2) evades the immune system.

The study was co-led by Dr. Arinjay Banerjee (PhD), a principal scientist and Canada Research Chair in Zoonotic Virus and Animal Reservoirs at the Vaccine and Infectious Disease Organization (VIDO) at the University of Saskatchewan (USask), and members of his lab, in partnership with the Overall lab at the University of British Columbia.

They found that while the virus can interfere with one of the body’s early defences, it may also unintentionally trigger another response that helps slow infection. The study was published in the journal Cell Reports today.

The team found that SARS-CoV-2 disrupts part of the cell’s early warning system, making it harder for the body to respond quickly to infection. But that same viral action may also set off a second protective response. In other words, even when the virus tries to shut down one defence mechanism, it may accidentally kickstart another.

These results prove that viruses can continue to spread by finding ways to get around the body’s defences before the immune system can stop them. Scientists around the world are working to better understand exactly how SARS-CoV-2 does that, and where its strategy has limits. Studies like this help reveal weak points that could one day lead to better antiviral treatments.

“Viruses are constantly trying to gain the upper hand over the body’s defences,” said Banerjee. “What makes this study exciting is that it shows SARS-CoV-2, specifically the main protease, may be able to interfere with one part of that defence, but not without triggering another response that helps the cell fight back. That gives us a better understanding of how infection works and may help point the way towards future antiviral strategies.”

Viruses by nature are complex and tricky to predict. Through this work, Banerjee and his team highlight how complex the interaction between viruses and the immune system can be. Rather than simply overpowering the body’s defences, viruses often face trade-offs. A move that helps them in one way may create a new vulnerability in another. That is exactly the kind of insight scientists look for when trying to better understand infection and identify new opportunities for intervention.

In the long term, the findings could help guide future antiviral research by giving scientists a clearer picture of how viruses like SARS-CoV-2, and potentially other coronaviruses, behave inside infected cells and where their strategies may fall short. The work adds to global efforts to better understand emerging viruses and strengthen our ability to respond to future infectious disease threats.