College of Medical, Veterinary & Life Sciences

Our genomes contain hundreds of genes with antiviral jobs, which are called into action when a virus succeeds in infecting one of our cells.

By acting cooperatively, these genes provide defence against a wide range of viruses, comprising what scientists refer to as the ‘innate immune system’.

However, viruses evolve more rapidly than we do, and many viruses have acquired their own genes (sometimes brazenly stolen from their animal hosts!) that counteract innate immunity. But does this mean that viruses always have the upper hand when it comes to infecting humans?

In a new study led by by the MRC-University of Glasgow Centre for Virus Research (CVR), scientists have discovered a cost-effective way that a human antiviral gene broadens the range of viruses that it can attack. The gene in question – called OAS2 – produces two versions of its protein. One protein version – known as an ‘isoform’ – targets the virus Cardiovirus A, or Encephalomyocarditis virus (EMCV), which can cause inflammation in the heart and brain. The second OAS2 isoform inhibits a common cold coronavirus – related to the virus that causes COVID-19.

The two OAS2 isoforms are 95% identical to one another, only differing by a short, disordered and flexible tail, which is only 4 amino acids long in one isoform, and 36 amino acids long in the other. The rest of the 683 amino acid OAS2 protein is the same between the two.

The researchers found that, despite their similarity, these two proteins use unique sets of molecular ‘tools’ to inhibit viral replication. Research is underway to define what these unique antiviral mechanisms are.

Mutations in the gene OAS2 and related antiviral enzymes can alter a person’s susceptibility to viral infections, with potentially severe consequences during the emergence of novel viruses like SARS-CoV-2 during the recent COVID-19 pandemic. People with mutations in the related OAS1 gene had increased likelihood of developing severe disease.

First author Dr Emma Davies, who co-led the study, said: “What really surprised us was that two forms of a protein, differing only by a tiny region, were able to inhibit completely different viruses in completely different ways. It’s a testament to how the immune system has evolved to maximise its antiviral arsenal.”

Dr Adam Fletcher, UKRI Future Leadership Senior Fellow at the CVR, who also co-led the study, said: “It is well known that genes can encode multiple different ‘versions’ of their proteins, but whether these subtle differences have functional consequences is often not known. The antiviral gene OAS2 provides a great example of how this process expands functional diversity from a single gene – a sort of, Buy One, Get One Free’ for the immune response”

The work was supported by multiple UKRI and MRC-funded projects and a Wellcome Trust Integrative Biology PhD Programme at the University of Glasgow. Undergraduates, MSc students and PhD students were all involved in the basic research.

The paper, ‘Alternative splicing broadens antiviral diversity at the human OAS2 locus,’ is published in The EMBO Journal. The first author is Dr Emma Davies and joint second authors were Ms Alegna Calderon Nuñez, MSc and Ms Allison Ward.

 

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Enquiries: ali.howard@glasgow.ac.uk or elizabeth.mcmeekin@glasgow.ac.uk

 

 

First published: 5 June 2026