Suidae iPSC-derived macrophages as models for investigating susceptibility and resilience to African swine fever virus

African swine fever virus (ASFV) causes a lethal hemorrhagic fever in pigs, and spread of this disease threatens many pig species (Suidae) globally. By contrast, ASFV infections in the natural evolved hosts, warthog and bushpig, are subclinical. The macrophage (Mϕ) is the primary target of ASFV, and species-dependent responses in Mϕs are presumed to influence disease susceptibility. In an attempt to model these differences in vitro, we generated transgene-regulated induced pluripotent stem cells (iPSCs) from domestic pig, wild boar, red river hog, and warthog and confirmed that their corresponding iPSC-derived Mϕs (iPSCdMs) supported infection and replication of ASFV. In contrast to the other species, however, warthog iPSCdMs did not induce interferon α upon infection by either virulent or attenuated ASFV. iPSCdMs may therefore represent an experimental system to understand how ASFV infection of Mϕs contributes to disease and aid development of strategies to combat this economically and environmentally devastating pathogen.