Temporally integrated transcriptome analysis reveals ASFV pathology and host response dynamics

African swine fever virus (ASFV) causes a lethal swine hemorrhagic disease and is currently responsible for widespread damage to the pig industry. The molecular mechanisms of ASFV pathogenicity and its interaction with host responses remain poorly understood. In this study, we profiled the temporal viral and host transcriptomes in porcine alveolar macrophages (PAMs) infected at 6, 12, 24 and 48 hours with highly virulent (SY18) and low virulent (HuB20) ASFV strains. We first identified profound differences in the virus expression programs between SY18 and HuB20, while the transcriptome dynamics in host cells were dominated by infection time. Through integrated computational analysis and experimental validation, we identified differentially expressed genes and related biological processes, and elaborated differential usage of the NF-kappaB related pathways by the two virus strains. In addition, we observed that compared to the highly virulent SY18 strain, HuB20 infection quickly activates expression of receptors, sensors, regulators, as well as downstream ef-fectors, including cGAS, STAT1/2, IRF9, MX1/2, suggesting rapid induction of a strong immune response. Lastly, we constructed a host-virus coexpression network, which shed light on pathogenic functions of several ASFV genes. Taken together, these results will provide a basis for further mechanistic studies on the functions of both viral and cellular genes that are involved in different responses.