Proteomic analysis of mitochondria in respiratory epithelial cells infected with human respiratory syncytial virus and functional implications for virus and cell biology

Diane Carolyn Munday, Gareth Howell, John N. Barr, Julian A. Hiscox

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

OBJECTIVES:
The aim of this study was to quantitatively characterise the mitochondrial proteome of airway epithelial cells infected with human respiratory syncytial virus (HRSV), a major cause of paediatric illness.
METHODS:
Quantitative proteomics, underpinned by stable isotope labelling with amino acids in cell culture, coupled to LC-MS/MS, was applied to mitochondrial fractions prepared from HRSV-infected and mock-infected cells 12 and 24 h post-infection. Datasets were analysed using ingenuity pathway analysis, and the results were validated and characterised using bioimaging, targeted inhibition and gene depletion.
KEY FINDINGS:
The data quantitatively indicated that antiviral signalling proteins converged on mitochondria during HRSV infection. The mitochondrial receptor protein Tom70 was found to act in an antiviral manner, while its chaperone, Hsp90, was confirmed to be a positive viral factor. Proteins associated with different organelles were also co-enriched in the mitochondrial fractions from HRSV-infected cells, suggesting that alterations in organelle dynamics and membrane associations occur during virus infection.
CONCLUSIONS:
Protein and pathway-specific alterations occur to the mitochondrial proteome in a spatial and temporal manner during HRSV infection, suggesting that this organelle may have altered functions. These could be targeted as part of potential therapeutic strategies to disrupt virus biology.
Original languageEnglish
Pages (from-to)300-318
Number of pages19
JournalJournal of Pharmacy and Pharmacology
Volume67
Issue number3
Early online date23 Dec 2014
DOIs
Publication statusPublished - 26 Mar 2015
EventBritish Council Researcher Links Workshop - Vietnam, Ho Chi Min, United Kingdom
Duration: 15 Feb 201425 Oct 2015

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