A proteomic approach towards the understanding of african swine fever pathogenicity

African swine fever, a highly lethal viral disease of swine (*Sus scrofa*), poses a threat to domestic and wild suids world-wide. Currently, neither vaccine nor treatment is available against its causative agent, African swine fever virus (ASFV). For this highly complex dsDNA virus numerous genomic variations affecting its virulence have been identified. However, the molecular basis of the different clinical outcomes is largely unknown. Using quantitative label-free mass spectrometry, we compared the proteomes of monocyte-derived macrophages after in-vitro infection with two closely related ASFV genotype II isolates of different pathogenicity, the highly pathogenic “Armenia 2008” and the moderately pathogenic “Estonia 2014” strains. The expression patterns of the viral proteins were very similar with the exception of the genes not present in ASFV “Estonia 2014” due to deletions within its genome. The observed host proteome response to infection was also very similar irrespective of the ASFV strain used. Pathway analysis showed that both strains impacted on the immune response and mitochondrial processes, and induced ER-stress.