African swine fever virus (ASFV) causes a lethal, haemorrhagic disease in domestic swine that threatens pig production across the globe. Unlike domestic pigs, warthogs, which are wildlife hosts of the virus, do not succumb to the lethal effects of infection. There are three amino acid differences between the sequence of the warthog and domestic pig ReLA protein; a subunit of the nf-κB transcription factor that plays a key role in regulating the immune response to infections. Domestic pigs with all 3 or 2 of the amino acids from the warthog RELA orthologue have been generated by gene editing. To assess if these variations confer resilience to ASF we established an intranasal challenge model with a moderately virulent ASFV. No difference in clinical, virological or pathological parameters were observed in domestic pigs with the 2 amino acid substitution. Domestic pigs with all 3 amino acids found in warthog RELA were not resilient to ASF but a delay in onset of clinical signs and less viral DNA in blood samples and nasal secretions was observed in some animals. Inclusion of these and additional warthog genetic traits into domestic pigs may be one way to assist in combating the devastating impact of ASFV. African swine fever virus (ASFV) is a large DNA virus and sole member of the family Asfarviridae that causes a mostly lethal haemorrhagic disease, African swine fever (ASF), in domestic pigs and Eurasian wild boar. ASFV can genetically be separated into 24 genotypes that cause the same disease, but immunological cross-protection is limited and poorly understood 1. The introduction of ASF into a country results in trade restrictions and pig losses, thus the disease has a high socioeconomic consequence for both commercial and backyard farmers 2. Accordingly, the spread of this disease is a serious concern for the global pig industry. Following the incursion of a genotype II ASFV into the Caucasus in 2007 the virus has spread through Russia, entered the European Union in 2014 and, in 2018, was detected for the first time in China. Since then the Chinese pig population has declined by at least 20% and ASFV has further spread across many countries in South East Asia 3,4. Combating this global threat is hampered by the lack of a vaccine and is particularly difficult in production systems with poor biosecurity which are more vulnerable to virus introduction and contact with wild suids 1. ASFV infects all members of the family Suidae, which as well as domestic pigs (Sus scrofa domesticus), wild boar (Sus scrofa spp) and others also includes bushpigs (Potamochoerus spp.) and warthogs (Phacochoerus spp.), which are considered natural reservoir hosts 5. In domestic pigs and wild boar acute and subacute forms dominate,