27 September 2023
By: Amelia Genis
A deficiency in pigs’ immune system is crucial for the African swine fever virus to replicate and cause infection.
This finding was made possible through Crispr-Cas9 techniques used by a team of researchers from the Friedrich Loeffler Institute, affiliated with the German government, and the Roslin Institute at the University of Edinburgh.
It is a breakthrough in the study of this virus because little is known about factors within host animals that allow African swine fever to replicate and spread. Crispr is a technique for editing DNA, and Cas9 is an enzyme used to “cut” DNA.
African swine fever has killed more than 200 million pigs worldwide. The disease is deadly to wild and domestic pigs, and there is no internationally approved vaccine or treatment.
The virus has a large DNA genome from which more than 160 virus proteins are produced in infected cells. Little is known about the function of many of these proteins, and it is also not clear which proteins the virus uses to enter the host animal’s cells.
To determine which genes the virus needs to replicate, a number of pig cells were edited to remove specific genes. In laboratory tests, researchers then examined how the different cells responded to the virus.
To identify the important host proteins, researchers at the Roslin Institute created a Crispr-Cas9 molecular base that allowed their German counterparts to individually remove all known genes in the pig genome then test those cell cultures for susceptibility to the virus.
They found that five genes – RFXANK, RFXAP, SLA-DMA, SLA-DMB and CIITA – are important for a productive swine fever infection.
These genes produce proteins that are associated with the immune response to infection. When they were removed, there were severe defects in how the swine fever virus replicated.
When researchers reintroduced the SLA-DMB gene into pig cells, the virus’s ability to replicate effectively was fully restored.
According to the researchers, this suggests that this gene plays an important role in the early stage of swine fever infection and may be a suitable target protein for the development of effective treatments.
“This exciting finding not only enhances our understanding of the biology of the African swine fever virus but may also enable the development of new control measures,” said Dr Katrin Pannhorst, a researcher at the Friedrich Loeffler Institute.
This discovery provides important new insights into the biology of the African swine fever virus upon which future research will be based.
