Comparative proteomic analysis reveals different responses in porcine lymph nodes to virulent and attenuated homologous African swine fever virus strains

Abstract

African swine fever (ASF) is a pathology of pigs against which there is no treatment or vaccine. Understanding the equilibrium between innate and adaptive protective responses and immune pathology might contribute to the development of strategies against ASFV. Here we compare, using a proteomic approach, the course of the in vivo infection caused by two homologous strains: the virulent E75 and the attenuated E75CV1. Our results show a progres‑ sive loss of proteins by day 7 post-infection (pi) with E75, refecting tissue destruction. Many signal pathways were afected by both infections but in diferent ways and extensions. Cytoskeletal remodelling and clathrin-endocytosis were afected by both isolates, while a greater number of proteins involved on infammatory and immunological pathways were altered by E75CV1. 14-3-3 mediated signalling, related to immunity and apoptosis, was inhibited by both isolates. The implication of the Rho GTPases by E75CV1 throughout infection is also evident. Early events refected the lack of E75 recognition by the immune system, an evasion strategy acquired by the virulent strains, and signifcant changes at 7 days post-infection (dpi), coinciding with the peak of infection and the time of death. The protein signature at day 31 pi with E75CV1 seems to refect events observed at 1 dpi, including the upregulation of proteosomal subunits and molecules described as autoantigens (vimentin, HSPB1, enolase and lymphocyte cytosolic protein 1), which allow the speculation that auto-antibodies could contribute to chronic ASFV infections. Therefore, the use of proteomics could help understand ASFV pathogenesis and immune protection, opening new avenues for future research.