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A virus’s guide to switching off our defences - and how to switch them on again

Dr Nigel Stevenson, Trinity College Dublin

When a virus lands into our bodies, the cells in our immune system normally respond by switching on the defences. But many viruses - possibly including the one that causes COVID-19 - can switch off the on switch, and this buys the viruses more time to establish an infection.

But the human scientists are on the case: Dr Nigel Stevenson and his Viral Immunology Lab have figured out that many different viruses attack a specific biochemical pathway in cells in order to switch off the defences, and they are now exploring the possibility that SARS-CoV-2 uses this trick too.

Dr Stevenson’s work has zoned in on the JAK-STAT pathway, a signal that cells use to activate a substance called Interferon. This in turn switches on many genes and activities in the cell (and surrounding cells) that stop the virus from establishing an infection.

“We have been able to show that the Hepatitis C Virus, HIV and a respiratory virus, called RSV, all do this, they stop the JAK-STAT signal and this means that cells don’t switch on the Interferon pathway and related activities, that would normally get rid of a virus,” explains Dr Stevenson, who has received SFI funding to support his research.

“We have now developed prototype therapeutics, designed to block the virus from targeting the pathway, which we are further testing.”

Recently, his lab has collaborated with scientists in Hong Kong and the United States, and they have discovered that coronaviruses MERS-CoV and SARS-CoV-1 switch off the cell’s defences in a similar way. And now, they are turning their attention to SARS-CoV-2, the virus that causes COVID-19.

“A PhD student in my lab, Yamei Zhang, has been doing excellent work on this,” says Dr Stevenson. “And by looking at the genetic material of the COVID-19 virus from strains around the world, we can see that this new coronavirus has the information in its RNA to target this pathway. As soon as we have investigated the mechanism by which SARS-CoV-2 blocks our anti-viral responses, we will develop and test medicines that restore natural immunity against CoronaVirus.”