Understanding differences in host responses to African swine fever virus

Pork is the second most consumed meat in the world and is projected to account for 34% of the global meat market by 2030. However, the global supply of pork is threatened by African swine fever (ASF). The ongoing ASF panzootic has resulted in the culling of millions of pigs worldwide and is currently spreading in Asia, Africa, Europe, and the Caribbean. In 2018, the causative ASF virus (ASFV) spread into China (the world's largest pork producer) resulting in a loss of at least half of the nation's pig herd. This destabilised global pork markets and resulted in huge economic losses of at least £26 billion. ASFV infects pigs and wild boar and is typically transmitted through exposure to infected animals and contaminated surfaces. Current ASF control methods involve strict biosecurity, movement control and culling of infected or exposed animals, but these are insufficient to control the spread globally. There are no safe and effective vaccines for ASF that are licensed for use in major pork producing countries; the lack of ASF viral and vaccine immunobiology research has hampered vaccine development. To develop robust strategies to control ASFV, host immunity mechanisms need to be identified. Multiple strains of ASFV exist in the field. Virulent ASFV induces severe disease in animals that results in death within ten days, whilst low virulent ASFV causes mild disease and animals typically recover after infection. Immunity to infection requires the participation of different immune cells in a complex and dynamic manner. My key goal is to identify mechanisms behind the different clinical outcomes induced by ASFV strains of high and low virulence by investigating the complex interactions between diverse immune cell populations in organs infected by these strains. Understanding these differences will allow me to identify cell populations and genes that are important for future ASFV control approaches. I will use organ-derived cultures to study the immune processes involved in ASFV infection to reduce animal use in research, which could be a model for future research. I will first compare the primary immune responses of pig immune cells to low and high virulent ASFV infection. This will identify cell populations that are important for the development of resilience to ASFV infection. Next, I will investigate the differences in cell death caused by low and high virulent ASFV strains. Infection with virulent ASFV results in death of many immune cell populations essential for long-term immunity. Hence, the identification of cell populations dying, either due to direct infection or as collateral damage, will be useful to determine which cell populations should be focussed on in future vaccine development and selective breeding studies for disease resilience. Lastly, I will identify genes that are involved in resilience and resistance to ASFV by using gene expression profiling methods on important immune cell subsets that contribute to ASFV immunity. Identification of genes contributing to ASFV immunity will help to develop a panel of genes to be considered in future development of ASF resilient animals through genetic selection or gene editing. My research will lead to a reduction of animals used in research due to better informed experiments and fill the gaps in immunobiology research needed to establish better ASF control methods (through vaccines or selective breeding). This will ultimately improve livestock health and provide stability for livelihoods and global food security.