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

Júber Herrera-Uribe,Ángela Moreno,Ángeles Jiménez-Marín,Juan J Garrido,Sonia Pina-Pedrero,Fernando Rodríguez,Anna Lacasta,Paula L Monteagudo

doi:10.1186/s13567-018-0585-z

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.

Highlights

African swine fever virus (ASFV) is the causal agent of a haemorrhagic and often-lethal porcine disease, African swine fever (ASF), which causes affected countries important economic losses
We extend these studies by presenting a comparative proteomic analysis using gastrohepatic lymph nodes (GLN) from pigs infected in vivo with either the attenuated E75CV1 strain or with E75, its parental virulent ASFV strain, at different days post-infection; a model system previously used to unmask some of the mechanisms involved in homologous protection against ASFV [16]
Two‐dimensional electrophoresis reveals differential protein expression kinetics after in vivoinfection with either virulent E75 or attenuated E75CV1 ASFV‐isolates To widen and deepen our understanding of the mechanisms underlying ASFV-pathogenesis and immune response to ASFV, we characterized the variation in GLN protein profiles of pigs infected with E75 and E75CV at different times post-infection using a 2-DE proteomics approach

Summary

Introduction

African swine fever virus (ASFV) is the causal agent of a haemorrhagic and often-lethal porcine disease, African swine fever (ASF), which causes affected countries important economic losses. The high complexity of ASFV, together with its tropism for the immune system of the host, complicates the understanding of ASF pathogenesis. Both ASFV-specific antibodies [4] and CD8+ T-cells [3, 14], have been postulated as key players in the protection against ASFV. The dual role of the immune system during ASFV infection becomes evident again during chronic ASF-infections, characterized by mild clinical signs associated, on occasions, with immunopathological processes, such as immune complexes and swine IgM, IgG and C1q depositions [15]. Swine macrophages are the main target for ASFV, and depending on multiple factors, including the virulence of the ASFV strain, the immune system can play a dual role during both, ASFV-protection and contributing to the virus pathogenesis. Infections with attenuated ASFV strains normally render subclinical infections that are rapidly recognized by the innate immune system and cleared from the body, yielding pigs capable of resisting homologous lethal challenge [16]

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Conclusion