Gene editing for PRRSV resistance in pigs

Precision engineering renders target cells of PRRSV resistant to infection with the virus.

Researchers have used advanced genetic techniques to produce pigs that are potentially resilient to Porcine reproductive and respiratory syndrome (PRRS).

Early tests have revealed that cells from the pigs are completely resistant to infection with both major subtypes of the virus that causes the disease. The animals are otherwise healthy and the change – introduced using gene editing technology – should not affect their ability to fight off other infections, the researchers say.

Studies have shown that the PRRS virus targets macrophages. A molecule on the surface of these cells called CD163 plays a key role in enabling the PRRS virus to establish an infection. The research team at the University of Edinburgh’s Roslin Institute, in collaboration with Genus, used a gene-editing tool called CRISPR/Cas9 to cut out a small section of the CD163 gene in the pigs’ DNA code.

Laboratory tests of cells from the pigs with the modified CD163 gene have confirmed that this change in the pig’s DNA blocks the virus from being able to cause infection. The next stage in the study will be to test whether the pigs are resistant to infection when exposed to the virus. The findings are reported in PLoS Pathogens.

“Genome-editing offers opportunities to boost food security by reducing waste and losses from infectious diseases, as well as improving animal welfare by reducing the burden of disease. Our results take us closer to realising these benefits and specifically address the most important infectious disease problem for the pig industry worldwide,” said Professor Alan Archibald, Head of Genetics and Genomics, The Roslin Institute

Previous studies by another team have produced pigs that lack the entire CD163 molecule, and which do not become ill when exposed to the PRRS virus. In the latest study, only the section of CD163 that interacts with the PRRS virus is removed and the molecule appears to retain its other functions.

PRRS is endemic in most pig producing countries worldwide. Vaccines have mostly failed to stop the spread of the virus, which continues to evolve rapidly. It is one of the greatest challenges facing pig producers today. In Europe alone, the disease is estimated to cost the pig industry more than €1.5 billion each year.

Article: Precision engineering for PRRSV resistance in pigs: Macrophages from genome edited pigs lacking CD163 SRCR5 domain are fully resistant to both PRRSV genotypes while maintaining biological function by Christine Burkard, Simon G. Lillico, Elizabeth Reid, Ben Jackson, Alan J. Mileham, Tahar Ait-Ali, C. Bruce A. Whitelaw and Alan L. Archibald, published in PLoS Pathogens (2017) 13(2): e1006206, doi:10.1371/journal.ppat.1006206