Abstract
Respiratory influenza virus infections represent a serious threat to human health. Underlying medical conditions and genetic make-up predispose some influenza patients to more severe forms of disease. To date, only a few studies have been performed in patients to correlate a selected group of cytokines and chemokines with influenza infection. Therefore, we evaluated the potential of a novel multiplex micro-proteomics technology, SOMAscan, to quantify proteins in the respiratory mucosa of influenza A and B infected individuals. The analysis included but was not limited to quantification of cytokines and chemokines detected in previous studies. SOMAscan quantified more than 1,000 secreted proteins in small nasal wash volumes from infected and healthy individuals. Our results illustrate the utility of micro-proteomic technology for analysis of proteins in small volumes of respiratory mucosal samples. Furthermore, when we compared nasal wash samples from influenza-infected patients with viral load ≥ 28 and increased IL-6 and CXCL10 to healthy controls, we identified 162 differentially-expressed proteins between the two groups. This number greatly exceeds the number of DEPs identified in previous studies in human influenza patients. Most of the identified proteins were associated with the host immune response to infection, and changes in protein levels of 151 of the DEPs were significantly correlated with viral load. Most important, SOMAscan identified differentially expressed proteins heretofore not associated with respiratory influenza infection in humans. Our study is the first report for the use of SOMAscan to screen nasal secretions. It establishes a precedent for micro-proteomic quantification of proteins that reflect ongoing response to respiratory infection.
Highlights
Each year, about 500 million people are infected by the influenza A virus (IAV) worldwide, of which about 500,000 die [1]
The samples included 18 from patients with identified influenza infection, 11 patients infected with IAV H3 strain, two infected with IAV pH1 subtypes, and five infected with influenza B
The imperfect principle component analysis (PCA) distribution of infected versus healthy patients is in part due to the small sample size and reflects the large uncontrollable heterogeneity which is an intrinsic property of human cohorts
Summary
About 500 million people are infected by the influenza A virus (IAV) worldwide, of which about 500,000 die [1]. Two subtypes, H5N1 and H7N9, may cause severe disease with lethal outcome [9,10,11,12,13] Adverse health conditions, such as obesity and diabetes, and genetic make-up predispose influenza patients to more severe forms of the disease [14,15,16,17,18,19]. Unraveling the pathogenesis of influenza in humans so as to identify potential targets for human therapeutics and predictors of disease severity necessitates the evaluation of the main site of viral replication, the mucosal tissues of the respiratory tract. The majority of the disease pathogenesis caused by influenza occurs after viral replication has already started to decline [21], adding to the impetus to develop host-response-targeted therapies in addition to continuing evaluation of better antiviral therapeutics. Quantitative mucosal biomarker identification is important for such work to proceed rationally
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
