While not quite the Colonel’s secret blend of 11 herbs and spices, scientists think they may have stumbled upon the correct formula to stop avian influenza virus from spreading in chicken cells grown in vitro. A collaboration of British researchers led by investigators at Imperial College London and the University of Edinburgh’s Roslin Institute, released data recently in eLife through an article titled “Species-specific differences in use of ANP32 proteins by influenza A virus,” in which they used the genome-editing technique CRISPR to delete a section of chicken DNA and prevent the virus from taking hold in the cells.

In the current study, the research team targeted a specific molecule inside chicken cells called ANP32A. Researchers at Imperial College London found that during an infection, flu viruses hijack this molecule to help replicate themselves. Working with experts from the Roslin Institute, the researchers used gene-editing techniques to remove the section of DNA responsible for producing ANP32A.

“We showed that the gene currently designated as avian ANP32B is evolutionarily distinct from mammalian ANP32B, and that chicken ANP32B does not support influenza A virus (IAV) polymerase activity even of human-adapted viruses,” the authors wrote. “Consequently, IAV relies solely on chicken ANP32A to support its replication in chicken cells. Amino acids 129I and 130N, accounted for the inactivity of chicken ANP32B. Transfer of these residues to chicken ANP32A abolished support of IAV polymerase.”

Avian flu is a major threat to farmed chickens worldwide, with severe strains killing up to 100% of birds in a flock. In rare instances, certain variations of the virus can infect people and cause serious illness. Efforts to control the spread of the disease are urgently needed.

“We have long known that chickens are a reservoir for flu viruses that might spark the next pandemic,” explained senior investigator Wendy Barclay, PhD, professor and chair in influenza virology at Imperial College London. “In this research, we have identified the smallest possible genetic change we can make to chickens that can help to stop the virus from taking hold. This has the potential to stop the next flu pandemic at its source.”

Researchers at The Roslin Institute previously worked with experts from Cambridge University to produce chickens that did not transmit bird flu to other chickens following infection, using genetic modification techniques. The new approach is different because it does not involve introducing new genetic material into the bird’s DNA.

While no avian flu resistant birds have been produced to date, the researchers say that the next step will be to try to produce chickens with the genetic change.

“This is an important advance that suggests we may be able to use gene-editing techniques to produce chickens that are resistant to bird flu,” concluded co-senior research investigator, Mike McGrew, PhD, senior lecturer at the Roslin Institute. “We haven’t produced any birds yet and we need to check if the DNA change has any other effects on the bird cells before we can take this next step.”

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