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 progressive loss of proteins by day 7 post-infection (pi) with E75, reflecting tissue destruction. Many signal pathways were affected by both infections but in different ways and extensions. Cytoskeletal remodelling and clathrin-endocytosis were affected by both isolates, while a greater number of proteins involved on inflammatory 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 reflected the lack of E75 recognition by the immune system, an evasion strategy acquired by the virulent strains, and significant 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 reflect 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.Electronic supplementary materialThe online version of this article (10.1186/s13567-018-0585-z) contains supplementary material, which is available to authorized users.

Host–virus interactions and defense mechanisms for giant viruses

“…Franzoni et al suspected that virulent viral isolates developed mechanisms to evade monocytes and macrophages responses, which likely consist of altered induction of an active immune response, hence promoting ASFV survival and pathogenesis. 148,150,151 The study of protein expression profiles in porcine lymph nodes confirmed that the virulent viral strain E75 and an attenuated viral strain E75CV1 were associated with different immunological patterns. Whereas infection with the attenuated E75CV1 strain was associated with an upregulation of genes encoding proteins involved in the activation of different innate immune pathways, infection with the virulent E75 strain was associated with the downregulation of the expression of genes encoding SERPINA3, induced during inflammation, or vitamin Dbinding protein involved in macrophage activation and inflammation.…”

Serum-Derived Extracellular Vesicles from African Swine Fever Virus-Infected Pigs Selectively Recruit Viral and Porcine Proteins

“…Most of these proteins are related to threonine endopeptidase activities, integrin and fibrinogen complexes and platelet activation and integrin-mediated signaling pathways. Previous reports about proteomic analysis after infection have been performed using either Vero cells or in vivo trials using gastro-hepatic lymph nodes exhibiting similar protein groups which were identified as over or sub-expressed, such as proteasome-related proteins, heat shock proteins or immunoglobulins [58,59], despite our focus on only extracellular vesicle-enriched fractions. Importantly, those results open a new path to explore the interactions between host cells and the virus, including the modulation of the immune system by different strategies including extracellular vesicles.…”

Understanding and combatting African Swine Fever

“…In contrast, Herrera-Uribe and co-workers analysed the proteome of lymph nodes from infected pigs. Ex vivo samples of organs are quite challenging for proteome analysis because of their higher heterogeneity, caused by the presence of different tissues (Herrera-Uribe et al, 2018). In this https://www.wageningenacademic.com/doi/book/10.3920/978-90-8686-910-7 -Wednesday, April 28, 2021 12:32:07 AM -CIRAD IP Address:193.51.114.14…”