TY - JOUR
T1 - Characterization of the plasma proteome of nonhuman primates during ebola virus disease or melioidosis
T2 - A host response comparison
AU - Ward, Michael D.
AU - Brueggemann, Ernst E.
AU - Kenny, Tara
AU - Reitstetter, Raven E.
AU - Mahone, Christopher R.
AU - Trevino, Sylvia
AU - Wetzel, Kelly
AU - Donnelly, Ginger C.
AU - Retterer, Cary
AU - Norgren, Robert B.
AU - Panchal, Rekha G.
AU - Warren, Travis K.
AU - Bavari, Sina
AU - Cazares, Lisa H.
N1 - Funding Information:
This project was supported by the Biomedical Advanced Research Development Authority (BARDA) IAA No. 750114PR9700011-0000 and DTRA plan# CB 10245.
Publisher Copyright:
© The Author(s) 2019.
PY - 2019
Y1 - 2019
N2 - Background: In-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 patho-genic 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 form-ing 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. Methods: Herein 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. Results: A 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 dynam-ics. 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. Conclusions: These 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.
AB - Background: In-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 patho-genic 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 form-ing 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. Methods: Herein 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. Results: A 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 dynam-ics. 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. Conclusions: These 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.
KW - Burkholderia pseudomallei
KW - Ebola virus
KW - Quantitative plasma proteomics
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UR - http://www.scopus.com/inward/citedby.url?scp=85086801659&partnerID=8YFLogxK
U2 - 10.1186/s12014-019-9227-3
DO - 10.1186/s12014-019-9227-3
M3 - Article
C2 - 30774579
AN - SCOPUS:85086801659
SN - 1542-6416
VL - 16
SP - 1
EP - 23
JO - Clinical Proteomics
JF - Clinical Proteomics
IS - 1
M1 - 7
ER -