Researchers find a key human gene that defends against avian flu

The BTN3A3 gene, commonly expressed in our airways, is vital to protecting humans against avian flu as most strains of the virus cannot get past its defences.

Researchers led by the MRC-University of Glasgow Centre for Virus Research (CVR) conducted a series of extensive tests as part of an international study into the pandemic potential of avian flu.

Through these tests, they were able to show that understanding the genetic make-up of currently circulating avian flu strains may offer one of the best lines of defence against widespread human transmission.

Avian flu

Avian flu, also commonly referred to as bird flu, primarily spreads among wild birds such as ducks and gulls and can also infect farmed and domestic birds such as chickens, turkeys and quails.

Since 2022 there has been a rise in bird flu cases around the world in both domestic and wild birds with major impacts on farmers worldwide.

‘Spillover’ to humans

While the disease mainly affects birds, it has been known to spill over into other species, including, in rare cases, humans.

For example, the 1918 Spanish flu virus, which caused more than 25 million deaths worldwide, is believed to have originated from an avian strain.

Keen to know why some avian flu transmission does occur in humans, the team behind this study compared the behaviour of hundreds of genes normally expressed by human cells during a viral infection with either human seasonal viruses or avian flu viruses.

The study showed that the BTN3A3 gene was able to block the replication of avian flu in human cells.

Escaping defences

While human infections with avian influenza are rare, some strains or subtypes are slightly more likely to lead to human infection. The team looked in more detail at one such strain, H7N9, which since 2013 has infected more than 1,500 individuals with 40% case fatality rate.

They were able to show that avian flu viruses like H7N9 have a genetic mutation that allows them to ‘escape’ the blocking effects of the BTN3A3 gene.

When studying the evolution of avian flu strains, the scientists were also able to show that there had been increases in the number of BTN3A3-resistant strains circulating in poultry around the same time as spill over events in humans.

One Health research

The One Health approach to research aims to ensure that human, animal, and environmental health questions are evaluated in an integrated and holistic manner to provide a more comprehensive understanding of problems and potential solutions.

Preparing for future disease threats in integrated and innovative ways is critical for our ability to effectively tackle infections that pose a threat to people, livestock, crops and natural resources.

Inform public health planning

Dr Stephen Oakeshott, Head of Infections and Immunity at the Medical Research Council (MRC) said:

This interesting study illustrates an important piece of the very complex puzzle underpinning viral transmission between species and shows the continued need for One Health research for infectious disease.

This type of mechanistic scientific insight, coupled with genetic surveillance, can offer a window into future disease risks to inform public health planning.

To read more about this research please visit the University of Glasgow website.

Further information

The study, ‘BTN3A3 evasion promotes the zoonotic potential of influenza A viruses’ is published in Nature.

Top image:  Credit: Wayne Marinovich, iStock, Getty Images Plus via Getty Images

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