Plasma Proteomic Analysis Distinguishes Severity Outcomes of Human Ebola Virus Disease

Abstract

Ebola virus (EBV) disease (EVD) is a highly virulent systemic disease characterized by an aggressive systemic inflammatory response and impaired vascular and coagulation systems, often leading to uncontrolled hemorrhaging and death. In this study, the proteomes of 38 sequential plasma samples from 12 confirmed EVD patients were analyzed. Of these 12 cases, 9 patients received treatment with interferon beta 1a (IFN-b-1a), 8 survived EVD, and 4 died; 2 of these 4 fatalities had received IFN-b-1a. Our analytical strategy combined three platforms targeting different plasma subproteomes: a liquid chromatography-mass spectrometry (LC-MS)-based analysis of the classical plasma proteome, a protocol that combines the depletion of abundant plasma proteins and LC-MS to detect less abundant plasma proteins, and an antibody-based cytokine/chemokine multiplex assay. These complementary platforms provided comprehensive data on 1,000 host and viral proteins. Examination of the early plasma proteomes revealed protein signatures that differentiated between fatalities and survivors. Moreover, IFN-b-1a treatment was associated with a distinct protein signature. Next, we examined those proteins whose abundances reflected viral load measurements and the disease course: resolution or progression. Our data identified a prognostic 4-protein biomarker panel (histone H1-5, moesin, kininogen 1, and ribosomal protein L35 [RPL35]) that predicted EVD outcomes more accurately than the onset viral load.