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Vaccines 2017, 5(4), 45; doi:10.3390/vaccines5040045

Detection of Nuclear Protein Profile Changes by Human Metapneumovirus M2-2 Protein Using Quantitative Differential Proteomics

1
Department of Pediatrics, University of Texas Medical Branch, Galveston, TX 77555, USA
2
Department of Plastic Surgery, TongJi Hospital, TongJi Medical College, Huazhong University of Science and Technology, Wuhan 430073, China
3
Department of Biochemistry, Baylor University, Waco, TX 76706, USA
4
Department of Pediatrics, TongJi Hospital, TongJi Medical College, Huazhong University of Science and Technology, Wuhan 430073, China
5
Department of Gynecologic Oncology Ward V, Hunan Cancer Hospital, Xiangya School of Medicine, Central South University, Changsha 410008, China
6
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555, USA
7
Sealy Center for Molecular Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA
8
The Institute of Translational Science, University of Texas Medical Branch, Galveston, TX 77555, USA
9
The Institute for Human Infections & Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Romain Paillot
Received: 13 October 2017 / Revised: 14 November 2017 / Accepted: 29 November 2017 / Published: 3 December 2017
View Full-Text   |   Download PDF [3209 KB, uploaded 3 December 2017]   |  

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. View Full-Text
Keywords: hMPV; M2-2 motif; proteomics hMPV; M2-2 motif; proteomics
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MDPI and ACS Style

Ren, Y.; Choi, E.; Zhang, K.; Chen, Y.; Ye, S.; Deng, X.; Zhang, K.; Bao, X. Detection of Nuclear Protein Profile Changes by Human Metapneumovirus M2-2 Protein Using Quantitative Differential Proteomics. Vaccines 2017, 5, 45.

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