@article{35b6fc274db445e2a78d0b24415d877c,
title = "Detection of nuclear protein profile changes by human metapneumovirus M2-2 protein using quantitative differential proteomics",
abstract = "Human metapneumovirus (hMPV) is a leading cause of lower respiratory infection in pediatric populations globally. This study examined proteomic profile changes in A549 cells infected with hMPV and two attenuated mutants with deleted PDZ domain-binding motif(s) in the M2-2 protein. These motifs are involved in the interruption of antiviral signaling, namely the interaction between the TNF receptor associated factor (TRAF) and mitochondrial antiviral-signaling (MAVS) proteins. The aim of this study was to provide insight into the overall and novel impact of M2-2 motifs on cellular responses via an unbiased comparison. Tandem mass tagging, stable isotope labeling, and high-resolution mass spectrometry were used for quantitative proteomic analysis. Using quantitative proteomics and Venn analysis, 1248 common proteins were detected in all infected samples of both technical sets. Hierarchical clustering of the differentiated proteome displayed distinct proteomic signatures that were controlled by the motif(s). Bioinformatics and experimental analysis confirmed the differentiated proteomes, revealed novel cellular biological events, and implicated key pathways controlled by hMPV M2-2 PDZ domain-binding motif(s). This provides further insight for evaluating M2-2 mutants as potent vaccine candidates.",
keywords = "HMPV, M2-2 motif, Proteomics",
author = "Yuping Ren and Eun-Jin Choi and Ke Zhang and Yu Chen and Sha Ye and Xiaoling Deng and Kangling Zhang and Xiaoyong Bao",
note = "Funding Information: Acknowledgments: All authors concur there are no conflicts of interest associated with this published work. This work was supported by grants from the National Institutes of Health-National Institute of Allergy and Infectious Diseases 1R01AI107033-01 and R21AI113771-01A1; the American Lung Association RG232529N; and American Heart Association 12BGIA12060008 to X.B. Authors thank Bethany J. Baker for assistance with manuscript editing. She is supported by the UTMB CTSA funded by NCATS grant UL1TR001439. We also thank Bruce A. Luxon, who retired as the director of UTMB Bioinformatics Program, for his advice on data analysis. Funding Information: All authors concur there are no conflicts of interest associated with this published work. This work was supported by grants from the National Institutes of Health-National Institute of Allergy and Infectious Diseases1R01AI107033-01 and R21AI113771-01A1; the American Lung AssociationRG232529N; and American Heart Association12BGIA12060008 to X.B. Authors thank Bethany J. Baker for assistance with manuscript editing. She is supported by the UTMB CTSA funded by NCATS grant UL1TR001439. We also thank Bruce A. Luxon, who retired as the director of UTMB Bioinformatics Program, for his advice on data analysis. Publisher Copyright: {\textcopyright} 2017 by the author. Licensee MDPI, Basel, Switzerland.",
year = "2017",
month = dec,
doi = "10.3390/vaccines5040045",
language = "English (US)",
volume = "5",
journal = "Vaccines",
issn = "2076-393X",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "4",
}