An international team of scientists has identified a gene that is preventing the bird flu viruses from spilling over into humans.In the study, published in the journal Nature, researchers revealed a human protein, BTN3A3, which inhibits a crucial step needed for viral replication of avian influenza A virus, also commonly referred to as bird flu.
Scientists led by the MRC-University of Glasgow Centre for Virus Research (CVR) found that BTN3A3 is commonly expressed in human airways, as a key human defence against avian flu.“We determined that BTN3A3 is expressed in human airways and its antiviral activity evolved in primates. We show that BTN3A3 restriction acts primarily at the early stages of the virus life cycle by inhibiting avian influenza A viruses RNA replication,” the researchers wrote in the paper.
Avian influenza A virus, also commonly referred to as bird flu, primarily spreads among wild birds such as ducks.Since 2022 there has been a rise in bird flu cases around the world in both domestic and wild birds.
The recent outbreak of avian influenza A (H5N1) virus has killed a record number of birds and also spread to otters, sea lions, foxes, dolphins and seals, cats among others.Scientists expect that bird flu that can cross the species barrier is expected to cause the next pandemic.
Although rare, influenza A viruses have occasionally infected humans. According to the World Health Organization (WHO), from 2003 to 2023, a total of 873 human cases of infection with influenza A (H5N1) and 458 deaths have been reported globally from 21 countries.
In the study, the researchers found that compared to seasonal human flu viruses, which infect the human population regularly, the BTN3A3 gene was able to block the replication of avian flu in human cells.
In the case of H7N9 virus, which since 2013 has infected more than 1,500 humans with 40 per cent case fatality rate, the team found these strains have a genetic mutation that allows them to ‘escape’ the blocking effects of the BTN3A3 gene.
Further, the researchers found 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.“Identifying BTN3A3 resistant variants when they first emerge in birds might help prevent human infections,” said Rute Maria Pinto, the first author of this study.
“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,” Pinto added.
The team also found that all the human influenza pandemics, including the devastating 1918-19 global flu pandemic and the swine flu pandemic in 2009 were caused by influenza viruses that were resistant to BTN3A3.
As a result, this study suggests that having resistance to this gene may be a key factor in whether any flu strain has human pandemic potential.“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,” said Professor Massimo Palmarini, Director of CVR.
“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,” he added.