2023-10-15 14:52:00
In a current study, researchers show that it is possible to make chickens more resistant to bird flu by making minimal changes to their genome. The great hope is that genetic modification, alongside contact avoidance and vaccinations, might be an approach to contain the H5N1 bird flu pandemic in the future. But experts still see many legal and practical hurdles.
So far, chickens have been defenseless once morest the H5N1 bird flu virus. The disease leads to their death following just a few days. If the virus is found in a herd, all animals usually have to be killed.
The virus has also adapted to native birds and is killing hundreds of thousands of wild animals. Chickens, ducks and chicks also have to be culled once more and once more in order to contain the spread of the virus. So far, avoiding contact with wild birds has been a central approach in the fight once morest the virus. It is also possible to vaccinate the animals, although this is only permitted in exceptional cases in this country and the EU. Researchers are therefore intensively looking for additional remedies once morest bird flu.
Now a new study from Great Britain gives hope: It shows that genetic modification can make chickens resistant to the bird flu virus. This might not only protect existing livestock populations from bird flu, but above all also limit the spread of the virus. The study is a so-called proof-of-concept, i.e. a general feasibility study.
Exchange of amino acids ensures resistance
Using genome editing, the researchers changed the host protein ANP32A. This is the protein that is essential for the virus to multiply in the chickens. The team swapped two amino acids in the protein. The result: With a low viral load, nine out of ten genetically modified chickens did not become infected. However, as the viral load increased, resistance decreased, according to the researchers. You cannot completely protect the animals with this method. It is said that complete resistance would be theoretically possible, but for this to happen all three genes in the ANP32 gene family would have to be changed. Experiments in cell culture have shown this. But switching off all three genes would probably be fatal for a chicken, according to the research team.
The British have now been able to show that it is in principle possible to create resistant poultry varieties using genome editing. But there are limitations here too: In one Guide for the environmental impact assessment of genetically modified animals The European Food Safety Authority (EFSA) points out risks. Accordingly, such animals might have a longer incubation period and might also behave more actively when infected, which would result in more pathogens being created and these might be transmitted for longer. Infected animals might therefore be recognized too late and possibly infect non-genetically modified chickens. In addition, the virus might mutate further and thereby circumvent resistance. And then of course the question arises as to whether the change in the genome might possibly have negative effects on animals and humans, it goes on to say. This has not yet been sufficiently researched.
Study also shows adaptability of viruses
The new study is generating great interest among experts. Stephan Ludwig, director at the Institute for Molecular Virology at the Westphalian Wilhelms University in Münster, says that the work simultaneously shows the opportunities and limitations of such an approach. “It is a very elegant work that shows the critical importance of the ANP32 gene family for the replication of avian influenza viruses in a complex organism.” It also shows that a well-thought-out gene editing strategy can be suitable for achieving robust resistance to infection. The resistance would also be passed on to the offspring. However, the study also shows the great adaptability of the viruses, says Ludwig, with breakthrough infections occurring in these initial experiments at high viral loads.
However, Ludwig notes that it is not certain whether the genetic modification will have an impact on the chicken. Although the researchers carried out a series of experiments to show that the mutations in ANP32A had no negative effects, the protein is still one that also has a function in uninfected cells, says Ludwig. “It is therefore entirely possible that a possible influence on the organism has not yet been recognized because it is not obvious at first glance.”
Free-range farming would not be possible for genetically modified chickens under the current legal situation. Image rights: IMAGO / Countrypixel
For Timm Harder, the laboratory manager at the Institute for Virus Diagnostics at the Friedrich Loeffler Institute, the question also arises regarding the efficiency of the approach. Although the changes prevented infections when a low dose of virus was used, resistance was broken at higher doses. The bulk of the viruses would have already contained virus variants that had mutations in order to circumvent the modified ANP32A protein. “In the further course, some of these mutations turned out to be identical to those that can also mediate increased adaptation to mammals or humans,” explains Harder. This is a critical point that might indicate that viruses exist that might develop further resistance-evading mutations.
Skepticism regarding practice
Nevertheless, virologist Ludwig believes that resistant chickens would help once morest the spread of bird flu – even if the global spread occurs via wild birds. “However, if the pathogens enter a poultry farm, it acts as an incubator and huge viral loads are generated, which promote further spread.” Therefore, robust genetic resistance in commercial poultry would be one way to contain the bird flu burden and the economic consequences, says Ludwig. “The virus from wild birds would not be a threat to the birds protected in this way.”
But the big hurdle, Ludwig from Münster believes, is the practice: “Without wanting to diminish the findings of the work, I am very skeptical as to whether such an approach can actually be implemented on a broad scale in the medium term,” he says. “We are talking here regarding a global spread of genetically modified animals, although the extent of both necessary and tolerated genetic changes required to achieve robust resistance is not yet at all clear.” Ludwig sees both legal and ethical hurdles – and also problems with the acceptance of the approach among the population. “In this respect, the work is initially an elegant academic exercise and is still far from being used in actual practice,” summarizes Ludwig.
Harder refers to EU law with regard to practice. Accordingly, organisms whose genomes have been modified using the CRISPR/Cas process are considered genetically modified organisms (GMOs), he explains. “Their use would therefore require genetic engineering approval and, according to current law, keeping them would only be possible in a genetic engineering facility. Free-range farming would then be equivalent to a release project.” In order to keep larger numbers of genetically modified chickens, legal adjustments would be necessary, says Harder.
Idoko-Akoh, Alewo et al.: Creating resistance to avian influenza infection through genome editing of the ANP32 gene family. Nature Communications 14, Article number: 6136 (2023). DOI: 10.1038/s41467-023-41476-3.
News
more on the subject
This topic in the program:MDR CURRENT | May 4, 2023 | 07:51 am
Show all
Show all
1697396990
#Chickens #protected #bird #flu #H5N1 #genetic #engineering
