Elevated l -threonine is a biomarker for Lassa fever and Ebola
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SHORT REPORT
Elevated l‑threonine is a biomarker for Lassa fever and Ebola Trevor V. Gale1,6, John S. Schieffelin2, Luis M. Branco3, Robert F. Garry1,3* and Donald S. Grant4,5*
Abstract Background: Lassa fever and Ebola are characterized by non-specific initial presentations that can progress to severe multisystem illnesses with high fatality rates. Samples from additional subjects are examined to extend and corroborate biomarkers with prognostic value for these diseases. Methods: Liquid Chromatography Mass Spectrometry metabolomics was used to identify and confirm metabolites disrupted in the blood of Lassa fever and Ebola patients. Authenticated standards are used to confirm the identify of key metabolites. Results: We confirm prior results by other investigators that the amino acid l-threonine is elevated during Ebola virus infection. l-Threonine is also elevated during Lassa virus infection. We also confirmed that platelet-activating factor (PAF) and molecules with PAF moiety are reduced in the blood of patients with fatal Lassa fever. Similar changes in PAF and PAF-like molecules were not observed in the blood of Ebola patients. Conclusions: Metabolomics may provide tools to identify pathways that are differentially affected during viral hemorrhagic fevers and guide development of diagnostics to monitor and predict outcome. Keywords: Lassa fever, Ebola, Viral hemorrhagic fevers, Liquid Chromatography Mass Spectrometry, l-Threonine, Metabolomics Background Select features within the metabolome may serve as biomarkers for disease severity/progression/outcome and lend themselves to the design of prognostic methods for viral diseases, such as Lassa fever and Ebola. We have previously characterized endogenous small molecules with prognostic value originating from the blood of febrile patients triaged to the Lassa fever ward in Kenema, Sierra Leone [1]. In an extraordinary multi-omics study Eisfeld and coworkers [2] demonstrated that levels of serum l-threonine were elevated in the blood of patients with Ebola, another severe viral hemorrhagic
fever (VHF). Prior research has shown that l-threonine has significance as a biomarker in infectious disease and inflammation. Previously, l-threonine has been reported as a biomarker for both tuberculosis [3] and malaria [4]. Our prior study identified multiple unknown metabolites as potential biomarkers of acute Lassa fever [1]. Inspired by the results of Eisfeld and coworkers [2] we corroborate l-threonine as a biomarker of acute Lassa fever. We also contrast levels of other select metabolites, including plate-activating factor (PAF) and PAF-like molecules, between Lassa fever and Ebola patients. Authenicate standards were used to confirm the identity of l-threonine and selected PAF-like molecules.
*Correspondence: [email protected]; [email protected] 1 Department of Microbiology and Immunology, Tulane University, 1430 Tulane Avenue, JBJ568, New Orleans, LA 70112, USA 4 Viral Hemorrhagic Fever Program, Kenema Government Hospital, Kenema, Sierra Le
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