Nasopharyngeal Protein Biomarkers of Acute Respiratory Virus Infection
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 dev...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2017-03-01
|
| Series: | EBioMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396417300749 |
| _version_ | 1818671795448840192 |
|---|---|
| author | Thomas W. Burke Ricardo Henao Erik Soderblom Ephraim L. Tsalik J. Will Thompson Micah T. McClain Marshall Nichols Bradly P. Nicholson Timothy Veldman Joseph E. Lucas M. Arthur Moseley Ronald B. Turner Robert Lambkin-Williams Alfred O. Hero, III Christopher W. Woods Geoffrey S. Ginsburg |
| author_facet | Thomas W. Burke Ricardo Henao Erik Soderblom Ephraim L. Tsalik J. Will Thompson Micah T. McClain Marshall Nichols Bradly P. Nicholson Timothy Veldman Joseph E. Lucas M. Arthur Moseley Ronald B. Turner Robert Lambkin-Williams Alfred O. Hero, III Christopher W. Woods Geoffrey S. Ginsburg |
| author_sort | Thomas W. Burke |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-17T07:29:41Z |
| format | Article |
| id | doaj.art-4680ef2cc41047b0b38e84b878e5e24d |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-17T07:29:41Z |
| publishDate | 2017-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-4680ef2cc41047b0b38e84b878e5e24d2022-12-21T21:58:31ZengElsevierEBioMedicine2352-39642017-03-0117C17218110.1016/j.ebiom.2017.02.015Nasopharyngeal Protein Biomarkers of Acute Respiratory Virus InfectionThomas W. Burke0Ricardo Henao1Erik Soderblom2Ephraim L. Tsalik3J. Will Thompson4Micah T. McClain5Marshall Nichols6Bradly P. Nicholson7Timothy Veldman8Joseph E. Lucas9M. Arthur Moseley10Ronald B. Turner11Robert Lambkin-Williams12Alfred O. Hero, III13Christopher W. Woods14Geoffrey S. Ginsburg15Center for Applied Genomics and Precision Medicine, Department of Medicine, Duke University, Durham, NC 27708, USACenter for Applied Genomics and Precision Medicine, Department of Medicine, Duke University, Durham, NC 27708, USAProteomics and Metabolomics Shared Resource, Duke University Medical Center, Durham, NC 27708, USACenter for Applied Genomics and Precision Medicine, Department of Medicine, Duke University, Durham, NC 27708, USAProteomics and Metabolomics Shared Resource, Duke University Medical Center, Durham, NC 27708, USACenter for Applied Genomics and Precision Medicine, Department of Medicine, Duke University, Durham, NC 27708, USACenter for Applied Genomics and Precision Medicine, Department of Medicine, Duke University, Durham, NC 27708, USADurham Veteran's Affairs Medical Center, Durham, NC 27705, USACenter for Applied Genomics and Precision Medicine, Department of Medicine, Duke University, Durham, NC 27708, USACenter for Applied Genomics and Precision Medicine, Department of Medicine, Duke University, Durham, NC 27708, USACenter for Applied Genomics and Precision Medicine, Department of Medicine, Duke University, Durham, NC 27708, USASchool of Medicine, University of Virginia, Charlottesville, VA 22908, USAhVIVO, London, United KingdomDepartment of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, MI 48109, USACenter for Applied Genomics and Precision Medicine, Department of Medicine, Duke University, Durham, NC 27708, USACenter for Applied Genomics and Precision Medicine, Department of Medicine, Duke University, Durham, NC 27708, USAInfection 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.http://www.sciencedirect.com/science/article/pii/S2352396417300749Infectious diseaseInfluenzaHuman rhinovirusProteomicsDiagnostic biomarker |
| spellingShingle | Thomas W. Burke Ricardo Henao Erik Soderblom Ephraim L. Tsalik J. Will Thompson Micah T. McClain Marshall Nichols Bradly P. Nicholson Timothy Veldman Joseph E. Lucas M. Arthur Moseley Ronald B. Turner Robert Lambkin-Williams Alfred O. Hero, III Christopher W. Woods Geoffrey S. Ginsburg Nasopharyngeal Protein Biomarkers of Acute Respiratory Virus Infection EBioMedicine Infectious disease Influenza Human rhinovirus Proteomics Diagnostic biomarker |
| title | Nasopharyngeal Protein Biomarkers of Acute Respiratory Virus Infection |
| title_full | Nasopharyngeal Protein Biomarkers of Acute Respiratory Virus Infection |
| title_fullStr | Nasopharyngeal Protein Biomarkers of Acute Respiratory Virus Infection |
| title_full_unstemmed | Nasopharyngeal Protein Biomarkers of Acute Respiratory Virus Infection |
| title_short | Nasopharyngeal Protein Biomarkers of Acute Respiratory Virus Infection |
| title_sort | nasopharyngeal protein biomarkers of acute respiratory virus infection |
| topic | Infectious disease Influenza Human rhinovirus Proteomics Diagnostic biomarker |
| url | http://www.sciencedirect.com/science/article/pii/S2352396417300749 |
| work_keys_str_mv | AT thomaswburke nasopharyngealproteinbiomarkersofacuterespiratoryvirusinfection AT ricardohenao nasopharyngealproteinbiomarkersofacuterespiratoryvirusinfection AT eriksoderblom nasopharyngealproteinbiomarkersofacuterespiratoryvirusinfection AT ephraimltsalik nasopharyngealproteinbiomarkersofacuterespiratoryvirusinfection AT jwillthompson nasopharyngealproteinbiomarkersofacuterespiratoryvirusinfection AT micahtmcclain nasopharyngealproteinbiomarkersofacuterespiratoryvirusinfection AT marshallnichols nasopharyngealproteinbiomarkersofacuterespiratoryvirusinfection AT bradlypnicholson nasopharyngealproteinbiomarkersofacuterespiratoryvirusinfection AT timothyveldman nasopharyngealproteinbiomarkersofacuterespiratoryvirusinfection AT josephelucas nasopharyngealproteinbiomarkersofacuterespiratoryvirusinfection AT marthurmoseley nasopharyngealproteinbiomarkersofacuterespiratoryvirusinfection AT ronaldbturner nasopharyngealproteinbiomarkersofacuterespiratoryvirusinfection AT robertlambkinwilliams nasopharyngealproteinbiomarkersofacuterespiratoryvirusinfection AT alfredoheroiii nasopharyngealproteinbiomarkersofacuterespiratoryvirusinfection AT christopherwwoods nasopharyngealproteinbiomarkersofacuterespiratoryvirusinfection AT geoffreysginsburg nasopharyngealproteinbiomarkersofacuterespiratoryvirusinfection |