Marion Tony, Elbahesh Husni, Thomas Paul G, DeVincenzo John P, Webby Richard, Schughart Klaus
University of Tennessee Health Science Center, Department of Microbiology, Immunology and Biochemistry, Memphis, United States of America.
Department of Immunology, St. Jude Children's Research Hospital, Memphis, United States of America.
PLoS One. 2016 Apr 18;11(4):e0153674. doi: 10.1371/journal.pone.0153674. eCollection 2016.
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 ≥ 2(8) 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.
呼吸道流感病毒感染对人类健康构成严重威胁。潜在的健康状况和基因组成使一些流感患者易患更严重的疾病形式。迄今为止，仅在少数患者中进行了一些研究，以将一组选定的细胞因子和趋化因子与流感感染相关联。因此，我们评估了一种新型多重微蛋白质组学技术SOMAscan在定量甲型和乙型流感感染个体呼吸道黏膜中蛋白质的潜力。该分析包括但不限于对先前研究中检测到的细胞因子和趋化因子进行定量。SOMAscan对感染个体和健康个体少量鼻腔灌洗液中的1000多种分泌蛋白进行了定量。我们的结果说明了微蛋白质组学技术在分析少量呼吸道黏膜样本中蛋白质的实用性。此外，当我们将病毒载量≥2(8)且白细胞介素-6和CXC趋化因子配体10升高的流感感染患者的鼻腔灌洗样本与健康对照进行比较时，我们在两组之间鉴定出162种差异表达蛋白。这个数字大大超过了先前在人类流感患者研究中鉴定出的差异表达蛋白的数量。大多数鉴定出的蛋白质与宿主对感染的免疫反应相关，并且151种差异表达蛋白的蛋白质水平变化与病毒载量显著相关。最重要的是，SOMAscan鉴定出了迄今为止与人类呼吸道流感感染无关的差异表达蛋白。我们的研究是首次使用SOMAscan筛选鼻腔分泌物的报告。它为反映对呼吸道感染持续反应的蛋白质的微蛋白质组学定量建立了先例。
