Host-pathogen interplay in African swine fever virus: Immune evasion and genetic resistance driving prevention and control strategies

Since the first described outbreak of African Swine Fever (ASF), which is caused by African swine fever virus (ASFV), in Kenya, over a century ago, no approved commercial vaccine is widely available to prevent the disease. Research has focused on two main aspects of the disease. Firstly, targeting the virus virulence factors by identifying proteins responsible for host immune evasion that can be targeted to develop vaccine candidates. Novel strategies, including mRNA-based vaccines and synthetic ASFV genomes with reverse genetics, enable safe, immunogenic, and rapid development of live-attenuated and subunit vaccine candidates. Secondly, by identifying host determinants that confer resistance to ASF. ASFV infects both domestic pigs and wild boars irrespective of age and breed, causing nearly 100 % mortality. Warthogs and bushpigs, natural hosts of ASFV, show no clinical signs despite developing viremia, likely due to distinct innate and adaptive immune responses, epigenetic modifications, and environmental factors. Genetic and epigenetic investigations of this tolerance, focusing on type I interferon (IFN) induction and NF-κB pathways, which are often targeted by viral immune evasion proteins. Understanding these interactions and genetic variations between tolerant/resistant and susceptible animals may guide vaccine development and the creation of tolerant/resistant breeds. This review covers the ASFV genome, transmission, pathogenesis, virus's immune evasion strategies, and the host immunological response against ASFV.