Characterization of the plasma proteome of nonhuman primates during Ebola virus disease or melioidosis: a host response comparison

Abstract

BackgroundIn-depth examination of the plasma proteomic response to infection with a wide variety of pathogens can assist in the development of new diagnostic paradigms, while providing insight into the interdependent pathogenic processes which encompass a host’s immunological and physiological responses. Ebola virus (EBOV) causes a highly lethal infection termed Ebola virus disease (EVD) in primates and humans. The Gram negative non-spore forming bacillus Burkholderia pseudomallei (Bp) causes melioidosis in primates and humans, characterized by severe pneumonia with high mortality. We sought to examine the host response to infection with these two bio-threat pathogens using established animal models to provide information on the feasibility of pre-symptomatic diagnosis, since the induction of host molecular signaling networks can occur before clinical presentation and pathogen detection.MethodsHerein we report the quantitative proteomic analysis of plasma collected at various times of disease progression from 10 EBOV-infected and 5 Bp-infected nonhuman primates (NHP). Our strategy employed high resolution LC–MS/MS and a peptide-tagging approach for relative protein quantitation. In each infection type, for all proteins with > 1.3 fold abundance change at any post-infection time point, a direct comparison was made with levels obtained from plasma collected daily from 5 naïve rhesus macaques, to determine the fold changes that were significant, and establish the natural variability of abundance for endogenous plasma proteins.ResultsA total of 41 plasma proteins displayed significant alterations in abundance during EBOV infection, and 28 proteins had altered levels during Bp infection, when compared to naïve NHPs. Many major acute phase proteins quantitated displayed similar fold-changes between the two infection types but exhibited different temporal dynamics. Proteins related to the clotting cascade, immune signaling and complement system exhibited significant differential abundance during infection with EBOV or Bp, indicating a specificity of the response.ConclusionsThese results advance our understanding of the global plasma proteomic response to EBOV and Bp infection in relevant primate models for human disease and provide insight into potential innate immune response differences between viral and bacterial infections.Electronic supplementary materialThe online version of this article (10.1186/s12014-019-9227-3) contains supplementary material, which is available to authorized users.

Ebola virus infection induces a type I interferon response and the shutdown of key liver functions in human iPSC-derived hepatocytes

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Helping doctors hasten COVID-19 treatment: Towards a rescue framework for the transfusion of best convalescent plasma to the most critical patients based on biological requirements via ml and novel MCDM methods

“…The CP of eligible donors in areas where an epidemic disease has broken out can offer specific, artificially obtained, passive immunity against the local infectious agent [18] . Plasma protein levels can readily be affected by bacterial and viral infections [19] . Identifying specific viral protein biomarkers is a possible strategy to identify sources and types of infection [20] .…”

“…Plasma protein levels can readily be affected by bacterial and viral infections [19] . However, specific viral protein biomarkers can be used to identify the source and type of infections [20] .…”

Differential gene expression by RNA-Seq in Sigma-2 Receptor/TMEM97 knockout cells reveals its role in complement activation and SARS-CoV-2 viral uptake

“…Amongst the top upregulated genes were C4BPB (logFC = 3.33) and C4BPA (logFC = 2.20), which are proteins responsible for regulating the complement cascade upon tissue damage and modulating the coagulation cascade through its interaction with protein S 24,34 . Previous studies have shown the importance of inhibition of C4BP in the context of pathogenic infections including IAV and ebola virus 27,37 . Our next step was to determine if the protein expression levels tracked the genetic expression levels of C4BP upregulation upon loss of sigma-2R/TMEM97.…”