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EBioMedicine. 2017 Mar;17:172-181. doi: 10.1016/j.ebiom.2017.02.015. Epub 2017 Feb 21.

Nasopharyngeal Protein Biomarkers of Acute Respiratory Virus Infection.

Author information

1
Center for Applied Genomics and Precision Medicine, Department of Medicine, Duke University, Durham, NC 27708, USA.
2
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.
3
Proteomics and Metabolomics Shared Resource, Duke University Medical Center, Durham, NC 27708, USA.
4
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.
5
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.
6
Durham Veteran's Affairs Medical Center, Durham, NC 27705, USA.
7
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.
8
School of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
9
hVIVO, London, United Kingdom.
10
Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, MI 48109, USA.
11
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.
12
Center for Applied Genomics and Precision Medicine, Department of Medicine, Duke University, Durham, NC 27708, USA. Electronic address: geoffrey.ginsburg@duke.edu.

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.

KEYWORDS:

Diagnostic biomarker; Human rhinovirus; Infectious disease; Influenza; Proteomics

PMID:
28238698
PMCID:
PMC5360578
DOI:
10.1016/j.ebiom.2017.02.015
[Indexed for MEDLINE]
Free PMC Article

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