‘A major discovery in the battle between a coronavirus and its host’
Researchers at Utrecht ľ¹Ï¸£ÀûÓ°ÊÓ unravel new mechanism used by viruses to suppress the antiviral stress response in cells
Years ago, researchers found a coronavirus in beluga whales which drew the attention of virologists at Utrecht ľ¹Ï¸£ÀûÓ°ÊÓ. Upon closer examination of that virus, they made the chance discovery that the virus synthesises a protein that can suppress a crucial antiviral stress reaction in cells. This turned out to be an entirely new mechanism, one which had never before been described. The study has been published in Nature Microbiology.
Once a virus has penetrated a host cell, the virus begins to replicate itself. During this process, all so-called ‘RNA viruses’ manufacture a fragment of genetic material that a cell will recognise as a sign of danger. This then triggers the activation of antiviral defence mechanisms. These defences include the creation of ‘messenger molecules’ to warn neighbouring cells and activate the immune system as well. What's more, the cell also has the ability to halt the synthesis of new proteins (known as the ‘stress response’). As a consequence, the virus is unable to create new proteins and thereby is unable to replicate itself.
Clever tricks
Viruses, in turn, have evolved all kinds of clever ways to circumvent or deactivate cellular antiviral defence mechanisms. ‘We were the first researchers in the world to identify a new mechanism used by viruses to prevent cells from switching off protein synthesis,’ says Frank van Kuppeveld, Professor of Virology at Utrecht ľ¹Ï¸£ÀûÓ°ÊÓ's Faculty of Veterinary Medicine and senior author. ‘This is a major discovery. We now have a better understanding of how a viral infection takes hold.’ While the researchers made their discovery looking at a coronavirus in beluga whales, the mechanism in question works in a great many hosts – including human cells. They are currently studying whether this viral protein might be used to promote protein expression in cells under stressful conditions.
In addition to Van Kuppeveld, UU virologists Huib Rabouw and Raoul de Groot also played vital roles in the research. Albert Heck, who is affiliated with the Utrecht Molecular Immunology Hub, conducted the analyses using mass spectrometry.
The paper was published in Nature Microbiology on 20 July.