A key human gene has been shown to prevent most strains of bird flu from causing infection in people.
The gene, known as BTN3A3, is commonly expressed in our airways. It offers a vital human defence against avian flu, with most strains of the virus unable to get past its defences.
Understanding the genetic make-up of currently circulating avian flu strains may offer one of the best lines of defence against widespread human transmission, experts say.
The ability to identify strains which are resistant to the effects of BTN3A3 could help to assess the risk of a potential pandemic in humans.
Rising threat
Avian flu, or 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 cases in both domestic and wild birds around the world.
While the disease mainly affects birds, it has been known to spill over into other species, including, in rare cases, humans.
An international team, led by the MRC-University of Glasgow Centre for Virus Research (CVR) and supported by the University of Edinburgh’s Roslin Institute, sought to understand why some avian flu can infect humans.
Blocking effects
Scientists compared hundreds of human genes for their ability to restrict either human seasonal viruses or avian flu viruses.
The study showed that BTN3A3 was able to block the replication of avian flu in human cells. In contrast, seasonal human flu viruses, which infect the population regularly, are resistant to BTN3A3, meaning it cannot successfully block them.
The team also looked at avian flu viruses that occasionally do infect humans. For example H7N9, which since 2013 has infected more than 1,500 individuals with a 40 per cent case fatality rate.
Researchers 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.
Previous outbreaks
When studying the evolution of avian flu strains, scientists were also able to show that there had been an increase in the number of BTN3A3-resistant strains circulating in poultry around the same time as spillover events in humans.
Tracking the history of influenza pandemics in humans, researchers were also able to link BTN3A3 resistance with key influenza virus types.
All human flu pandemics, including the 1918 outbreak that caused over 25 million deaths worldwide and the swine flu pandemic of 2009, were caused by flu viruses that were resistant to BTN3A3.
The findings suggest that having resistance to this gene may be a key factor in whether any flu strain has human pandemic potential, experts say.
Identifying BTN3A3 resistant variants when they first emerge in birds might help prevent human infections. Control measures against emerging avian flu viruses can be tailored specifically against those that are BTN3A3-resistant, in addition to other genetic traits known to be important for zoonotic transmission.
We know that most emerging viruses with human pandemic potential come from animals. It is therefore critical to understand which genetic barriers might block an animal virus from replicating in human cells, thereby preventing infection.
Of course, viruses are constantly changing and can potentially overcome some of these barriers by mutating over time. This is why virus genetic surveillance will be crucial to help us better understand and control the spread of viruses with zoonotic and pandemic potential.
The study, published in Nature, was funded primarily by the Medical Research Council (MRC), and in part by the Wellcome Trust, BBSRC, NSERC (Canada), EU Horizon2020, and Medical Research Scotland.
