Nasopharyngeal Protein Biomarkers of Acute Respiratory Virus Infection

• Published in: EBioMedicine 2017-03, Vol.17 (C), p.172-181
• Main Authors: Burke, Thomas W., Henao, Ricardo, Soderblom, Erik, Tsalik, Ephraim L., Thompson, J. Will, McClain, Micah T., Nichols, Marshall, Nicholson, Bradly P., Veldman, Timothy, Lucas, Joseph E., Moseley, M. Arthur, Turner, Ronald B., Lambkin-Williams, Robert, Hero, Alfred O., Woods, Christopher W., Ginsburg, Geoffrey S.
• Format: Article
• Language: English
• Subjects: Biomarkers - metabolism; Diagnostic biomarker; Human rhinovirus; Humans; Infectious disease; Influenza; Influenza A Virus, H3N2 Subtype - pathogenicity; Influenza, Human - diagnosis; Influenza, Human - virology; Mass Spectrometry; Proteome - chemistry; Proteome - metabolism; Proteomics; Research Paper; Respiratory Mucosa - metabolism; Rhinovirus - pathogenicity
• ISSN: 2352-3964; 2352-3964
• DOI: 10.1016/j.ebiom.2017.02.015

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. •Acute respiratory virus infection triggers a complex response in the affected host.•Nasal proteomic methods were used to discover protein biomarkers characteristic of this host response.•A set of these proteins form a signature that accurately classifies respiratory viral infection. Acute respiratory viral infections are among the most common reasons for patient visits to primary and acute care settings, and represents a substantial burden on the health care system. Improved approaches to diagnose acute respiratory virus infections could decrease inappropriate antibacterial use and provide care-providers with critical information needed to guide treatment. Using a human viral challenge model, we have discovered and independently validated nasal proteins that are capable of classifying human influenza A and human rhinovirus infection from uninfected individuals with high accuracy.