Tom M Watson, Lynnette C Goatley, Stephen Meek, Lel Eory, Sylvia Kohler, Nicholas Berkley, Sofia Sternberg, Melany Jackson, Amy Findlay, Isabella Hoskins, Simon Girling, Joseph Mee, Alan L Archibald, Finn Grey, Falko Steinbach, Helen Crooke, Christopher L Netherton, Tom Burdon
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.