Pathogenesis and Immune Dynamics of African Swine Fever Virus Across Diverse Suid Species

African swine fever virus (ASFV) causes a severe hemorrhagic disease in Eurasian suids, whereas African suids are considered susceptible, but resistant to disease. To investigate the basis of this differential clinical fate, domestic pigs, Eurasian wild boar, red river hogs and common warthogs were inoculated with the virulent ASFV strain Armenia08. Host responses to ASFV infection were characterized using classical virological and immunological methods, supplemented by pathology and multi-omics analyses integrating single-cell RNA sequencing, transcriptomics and proteomics. Domestic pigs and wild boar developed acute-lethal disease with high viraemia, while red river hogs and warthogs remained clinically unaffected despite detectable viral replication. Disease severity correlated with the abundance of ASFV-positive monocytes and pronounced inflammatory signatures in Eurasian suids. By contrast, African suids exhibited limited monocyte infection, preserved MHC class II-mediated antigen presentation, and myeloid cell composition. These findings identify coordinated immune regulation and restricted monocyte vulnerability to viral immune evasion mechanisms as key features underlying ASFV tolerance in African suids.