title: Nasopharyngeal Protein Biomarkers of Acute Respiratory Virus Infection.
abstract: Infection of respiratory mucosa with viral pathogens triggers complex immunologic events in the affected host. We sought to characterize this response through proteomic analysis of nasopharyngeal lavage in human subjects experimentally challenged with influenza A/H3N2 or human rhinovirus, and to develop targeted assays measuring peptides involved in this host response allowing classification of acute respiratory virus infection. Unbiased proteomic discovery analysis identified 3285 peptides corresponding to 438 unique proteins, and revealed that infection with H3N2 induces significant alterations in protein expression. These include proteins involved in acute inflammatory response, innate immune response, and the complement cascade. These data provide insights into the nature of the biological response to viral infection of the upper respiratory tract, and the proteins that are dysregulated by viral infection form the basis of signature that accurately classifies the infected state. Verification of this signature using targeted mass spectrometry in independent cohorts of subjects challenged with influenza or rhinovirus demonstrates that it performs with high accuracy (0.8623 AUROC, 75% TPR, 97.46% TNR). With further development as a clinical diagnostic, this signature may have utility in rapid screening for emerging infections, avoidance of inappropriate antibacterial therapy, and more rapid implementation of appropriate therapeutic and public health strategies.
authors.affiliation: Center for Applied Genomics and Precision Medicine, Department of Medicine, Duke University, Durham, NC 27708, USA.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Burke
authors.affiliation: Center for Applied Genomics and Precision Medicine, Department of Medicine, Duke University, Durham, NC 27708, USA; Department of Electrical and Computer Engineering, Duke University, Durham, NC 27708, USA.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Henao
authors.affiliation: Proteomics and Metabolomics Shared Resource, Duke University Medical Center, Durham, NC 27708, USA.
authors.forename: Erik
authors.initials: E
authors.lastname: Soderblom
authors.affiliation: Center for Applied Genomics and Precision Medicine, Department of Medicine, Duke University, Durham, NC 27708, USA; Durham Veteran's Affairs Medical Center, Durham, NC 27705, USA; Division of Infectious Diseases and International Health, Department of Medicine, Duke University, Durham, NC 27710, USA.
authors.forename: Ephraim L
authors.initials: EL
authors.lastname: Tsalik
authors.affiliation: Proteomics and Metabolomics Shared Resource, Duke University Medical Center, Durham, NC 27708, USA.
authors.forename: J Will
authors.initials: JW
authors.lastname: Thompson
authors.affiliation: Center for Applied Genomics and Precision Medicine, Department of Medicine, Duke University, Durham, NC 27708, USA; Division of Infectious Diseases and International Health, Department of Medicine, Duke University, Durham, NC 27710, USA; Section for Infectious Diseases, Medicine Service, Durham Veteran's Affairs Medical Center, Durham, NC 27705, USA.
authors.forename: Micah T
authors.initials: MT
authors.lastname: McClain
authors.affiliation: Center for Applied Genomics and Precision Medicine, Department of Medicine, Duke University, Durham, NC 27708, USA.
authors.forename: Marshall
authors.initials: M
authors.lastname: Nichols
authors.affiliation: Durham Veteran's Affairs Medical Center, Durham, NC 27705, USA.
authors.forename: Bradly P
authors.initials: BP
authors.lastname: Nicholson
authors.affiliation: Center for Applied Genomics and Precision Medicine, Department of Medicine, Duke University, Durham, NC 27708, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Veldman
authors.affiliation: Center for Applied Genomics and Precision Medicine, Department of Medicine, Duke University, Durham, NC 27708, USA; Department of Electrical and Computer Engineering, Duke University, Durham, NC 27708, USA.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Lucas
authors.affiliation: Center for Applied Genomics and Precision Medicine, Department of Medicine, Duke University, Durham, NC 27708, USA; Proteomics and Metabolomics Shared Resource, Duke University Medical Center, Durham, NC 27708, USA.
authors.forename: M Arthur
authors.initials: MA
authors.lastname: Moseley
authors.affiliation: School of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Turner
authors.affiliation: hVIVO, London, United Kingdom.
authors.forename: Robert
authors.initials: R
authors.lastname: Lambkin-Williams
authors.affiliation: Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Alfred O
authors.initials: AO
authors.lastname: Hero
authors.affiliation: Center for Applied Genomics and Precision Medicine, Department of Medicine, Duke University, Durham, NC 27708, USA; Division of Infectious Diseases and International Health, Department of Medicine, Duke University, Durham, NC 27710, USA; Section for Infectious Diseases, Medicine Service, Durham Veteran's Affairs Medical Center, Durham, NC 27705, USA. Electronic address: chris.woods@duke.edu.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Woods
authors.affiliation: Center for Applied Genomics and Precision Medicine, Department of Medicine, Duke University, Durham, NC 27708, USA. Electronic address: geoffrey.ginsburg@duke.edu.
authors.forename: Geoffrey S
authors.initials: GS
authors.lastname: Ginsburg
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000472:pathogenicity; D007251:Influenza, Human / Q000175:diagnosis* / Q000821:virology; D013058:Mass Spectrometry; D020543:Proteome / Q000737:chemistry / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000378:metabolism*; D012229:Rhinovirus / Q000472:pathogenicity
chemical_list: D015415:Biomarkers; D020543:Proteome
keywords: Diagnostic biomarker; Human rhinovirus; Infectious disease; Influenza; Proteomics