Classical swine fever can spread quickly and uncontrollably among pigs, leading to high morbidity and mortality rates. A study now suggests a new way to remedy the situation: a small intervention in the genome makes pigs completely resistant to the virus. If the researchers used the CRISPR/Cas gene scissors to change just a single amino acid in a protein that is essential for the virus to multiply, the pigs remained healthy and passed on the resistance to their offspring. In Europe, however, genetically modified animals are not yet allowed to be used for food production.
The classical swine fever virus (CSFV) belongs to the genus of pestiviruses and is closely related to the pathogens causing bovine viral diarrhea (BVD) in cattle and border disease in sheep. It is not only transmitted from animal to animal, but also through contaminated slaughter products and waste, transport vehicles and objects. During outbreaks, millions of animals often fall victim to the disease – either through direct infection with the usually fatal disease or through culling orders that are ordered to contain the further spread. The economic damage is rising, sometimes amounting to billions.
Precise change
A team led by Helen Crooke from the British Animal and Plant Health Agency has now found a way to genetically modify pigs so that they become completely resistant to swine fever. To do this, the researchers built on the knowledge that the virus relies on a specific protein called DNAJC14 in its target cells in order to be able to reproduce in the pigs’ bodies. Previous studies on cell cultures had already suggested that it is enough to replace a single amino acid in this protein so that the virus can no longer use the protein for its replication.
With the help of the CRISPR/Cas gene scissors, Crooke and her colleagues now modified the genome of pigs so that exactly this amino acid was replaced. This made the protein useless for the virus, but otherwise remained fully functional. The pigs modified in this way developed normally and showed no health problems. When the researchers tried to infect these pigs with the swine fever virus, they showed no symptoms of infection. No viruses could be detected in the animals’ blood or organs. Accordingly, there was no immune reaction: the pigs’ leukocyte count remained at a normal level and they did not produce any antibodies against the virus. “These results show that the genetically modified pigs were completely resistant to infection,” says Konrad Fischer from the Technical University of Munich, who was not involved in the study.
Harmless for consumers
Further experiments showed that the pigs also passed on the resistance to their offspring. “Resistance to the virus should be permanent because the modified gene is inherited and its function is essential for the virus to multiply,” says Fischer. “Although in nature there is always a certain risk that viruses adapt to new conditions through mutations, in this case this is unlikely because DNAJC14 plays a central role in the viral cycle that is conserved across many species.” Rare variants of pestiviruses that can reproduce without the DNAJC14 protein have so far hardly become established in nature.
Consuming meat from genetically modified pigs would be harmless for consumers, says Nicolas Ruggli, who heads the swine viral infections department at the Swiss Federal Department of the Interior and was also not involved in the study. “There is simply a small piece of gene missing from the pig’s genome, without any foreign genes having been introduced,” he explains. “It is important to ensure that the small defect in the genetic material does not have any undesirable consequences for the animal, for example in terms of health, animal welfare or sensitivity to other diseases and pathogens.”
Vaccination, culling or genetic modification?
In the United States and parts of South America, certain genetically modified pigs are already approved for food production. Thanks to a genetic modification, these animals are resistant to the porcine reproductive and respiratory syndrome virus (PRRSV). In the European Union, however, no food or feed made from genetically modified animals can currently be sold. The extent of the agricultural and economic benefit of pigs that are genetically resistant to swine fever is still unclear. “From an agricultural perspective, such animals are extremely interesting,” says Fischer. “Classical swine fever continues to represent an enormous risk for pig populations and, in the event of an epidemic, often leads to the complete killing of entire herds. Genetically resistant animals could prevent major losses here.”
Ruggli, on the other hand, points out that vaccines are also available against classical swine fever, which, although not prophylactic, can be used in the event of an outbreak. “The vaccines are so efficient that the epidemic has now been limited to Central/South America and Asia,” says Ruggli. “In my opinion, culling in combination with vaccination is the better control measure for classical swine fever. It should be examined whether CSF-resistant pigs in endemic areas, together with vaccination, could help control the disease.” However, there are currently neither efficient and safe vaccines nor approaches to generating genetic resistance against African swine fever (ASF), which is currently causing cases in Germany.
“Overall, the study shows that targeted genetic modifications are a promising, modern way to develop long-term resistant livestock,” says Fischer. “This method can improve animal welfare, reduce production losses and make agriculture more resilient to infectious diseases.”
Source: Helen Crooke (Animal and Plant Health Agency, UK) et al., Trends in Biotechnology