Developing stem cell-derived macrophages to study host pathogen interactions and advance strategies to combat globally important disease in the pig

African Swine Fever Virus (ASFV) and Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) are currently responsible for unparalleled financial losses and welfare concerns in commercial pig farming across the world. ASFV causes a lethal haemorrhagic fever that, in the absence of an effective vaccine, necessitates strict containment and mass culling to eradicate disease. PRRSV is less virulent but is widespread in pig herds and causes infertility and respiratory problems that make PRRS the most costly viral disease in commercial pig farming. Both viruses preferentially infect pig macrophages and studying these viruses until now has relied on primary macrophage cultures or transformed cell lines: both of which have major limitations. To overcome this limitation we have developed a stem cell-based culture system for producing normal pig
macrophages that are readily infected with ASFV and PRRSV. We propose that macrophages generated from pig stem cell lines provide a biologically relevant and scalable system for ASFV/PRRSV research and vaccine development, significantly reducing the requirement for pigs as either a source of ex vivo macrophages, or as subjects in viral challenge experiments.

The aim of this programme is to maximise the efficiency of generating pig macrophages in culture by 1) Optimising macrophage differentiation using haematopoietic/macrophage reporter cell lines to characterise, monitor and refine the differentiation process, and 2) Deriving conditionally immortalised macrophage progenitor cell lines. Reporter activity and transcriptional profiling of key stages in stem cell-macrophage differentiation will inform rational development of optimised protocols and facilitate the establishment of new pig macrophages progenitor cell lines. This novel stem cell based platform will reduce the number of pigs required in ASFV/PRRSV research and will illustrate the potential for applying stem cell-based technology more generally in livestock research.

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Project grant

Status:

Not yet active

Principal investigator

Dr Thomas Burdon

Institution

University of Edinburgh

Co-Investigator

Dr Christine Tait-Burkard
Professor Lesley Forrester

Grant reference number

NC/V001140/1

Award date:

Sep 2020 - Aug 2022

Grant amount

£350,989