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PMID: 20647383 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Quantitative proteomic analysis of A549 cells infected with human respiratory syncytial virus.

Molecular & cellular proteomics : MCP ·Vol. 9 ·No. 11 ·2010-11-00 ·Pages 2438-59

Munday DC, Emmott E, Surtees R, Lardeau CH, Wu W, Duprex WP, Dove BK, Barr JN, Hiscox JA

Abstract

Human respiratory syncytial virus (HRSV) is a major cause of pediatric lower respiratory tract disease to which there is no vaccine or efficacious chemotherapeutic strategy. Although RNA synthesis and virus assembly occur in the cytoplasm, HRSV is known to induce nuclear responses in the host cell as replication alters global gene expression. Quantitative proteomics was used to take an unbiased overview of the protein changes in transformed human alveolar basal epithelial cells infected with HRSV. Underpinning this was the use of stable isotope labeling with amino acids in cell culture coupled to LC-MS/MS, which allowed the direct and simultaneous identification and quantification of both cellular and viral proteins. To reduce sample complexity and increase data return on potential protein localization, cells were fractionated into nuclear and cytoplasmic extracts. This resulted in the identification of 1,140 cellular proteins and six viral proteins. The proteomics data were analyzed using Ingenuity Pathways Analysis to identify defined canonical pathways and functional groupings. Selected data were validated using Western blot, direct and indirect immunofluorescence confocal microscopy, and functional assays. The study served to validate and expand upon known HRSV-host cell interactions, including those associated with the antiviral response and alterations in subnuclear structures such as the nucleolus and ND10 (promyelocytic leukemia bodies). In addition, novel changes were observed in mitochondrial proteins and functions, cell cycle regulatory molecules, nuclear pore complex proteins and nucleocytoplasmic trafficking proteins. These data shed light into how the cell is potentially altered to create conditions more favorable for infection. Additionally, the study highlights the application and advantage of stable isotope labeling with amino acids in cell culture coupled to LC-MS/MS for the analysis of virus-host interactions.

MeSH Terms
Cell Line/virology Chromatography, Liquid/methods Humans Isotope Labeling Pneumovirus Infections/metabolism Proteome/analysis Proteomics/methods Respiratory Syncytial Virus, Human/chemistry Tandem Mass Spectrometry/methods Viral Proteins/analysis
Chemicals
Proteome Viral Proteins
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Munday Diane C
Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom.
Emmott Edward
Surtees Rebecca
Lardeau Charles-Hugues
Wu Weining
Duprex W Paul
Dove Brian K
Barr John N
Hiscox Julian A
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Article Info
Journal
Molecular & cellular proteomics : MCP
Abbr.
Mol Cell Proteomics
ISSN
1535-9484
DOI
10.1074/mcp.M110.001859
Published
2010-11-00
Epub
2010-00-20
Pages
2438-59
Language
English
Region
United States
NLM ID
101125647
PMCID
PMC2984239
Subset
IM
Grants
Wellcome Trust · United Kingdom
Biotechnology and Biological Sciences Research Council · United Kingdom
Medical Research Council · G0801001 · United Kingdom
External Links
PubMed source DOI: 10.1074/mcp.M110.001859 PMC Full Text View journal details
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