Researchers at The Pirbright Institute have contributed to the development of a new method to generate pig immune cells on demand, providing a valuable platform for research into African swine fever virus (ASFV).
The approach enables scientists to produce macrophages - the immune cells targeted by ASFV - from both domestic and wild pig species. The system provides a platform to enable scientists to study how domestic and wild pigs respond to infection by the virus, and why wild African pigs show limited signs of illness while domestic pigs develop severe, often fatal disease.
Their efforts could inform the development of farmed pigs that are resilient to disease and determine whether pigs could be enabled to be entirely resistant to infection.
The study, carried out in collaboration with the Roslin Institute, the Friedrich-Loeffler Institute, the Animal and Plant Health Agency and the Royal Zoological Society of Scotland, was published in Stem Cell Reports.
Dr Chris Netherton, Group Leader at The Pirbright Institute, highlighted the significance of the new platform for ASFV research.
“The ability to study ASFV in biologically relevant cells from different species that have differing outcomes after infection offers the opportunity for a whole new approach to tackling this devastating disease.”
The team took tissue from domestic pigs, wild boar, red river hogs and warthogs and used it to generate induced pluripotent stem cells, which are in an early stage of development and have the capacity to develop into various tissue types. These stem cells were then developed into macrophages, a type of immune cell targeted by ASFV.
As macrophages cannot be cultured long-term in the laboratory, the stem cell approach provides a renewable source of these cells, allowing stem cells to be stored and developed into macrophages as required.
Dr Tom Burdon, the Roslin Institute, said:
“A consistently available source of macrophage immune cells represents a significant development for the study of infection and immunity without reliance on animals for research.”
Tests in the laboratory showed that immune cells from all four species supported the infection and replication of the virus, validating their usefulness as laboratory tools.
The researchers also found a suppressed immune response in warthog macrophages compared with the immune overreaction experienced by domestic pigs, indicating that this might contribute to the absence of clinical signs of infection and the resilience of these wild African relatives of domestic pigs.
Dr Lynnette Goatley, Postdoctoral Scientist at The Pirbright Institute, said the new approach could help overcome barriers to studying ASFV in different pig species.
“Comparative studies of ASFV-host interactions in species such as warthogs, red river hogs, and potentially rarer suids are limited by the ethical and logistical challenges associated with sample collection. The ability to generate iPSC-derived macrophages overcomes these barriers and represents a major advance for ASFV research.”
Scientists hope their technology will aid understanding of African swine fever (ASF) infection in domestic pigs, supporting the development of ways to mitigate disease and potentially breed pigs that are resistant to infection.
Dr Tom Watson, the Roslin Institute, said:
"ASF is devastating to domestic pigs, but has little impact on their wild African cousins and the key to understanding this lies in the immune cells that are the target of the virus across all pig species. Our development of a method to produce immune cells on demand will be useful in the study of this complex virus and will support research into these types of immune cells more broadly."
Read the paper: Suidae iPSC-derived macrophages as models for investigating susceptibility and resilience to African swine fever virus