Quantitative Proteomic Analysis of A549 Cells Infected with Human Respiratory Syncytial Virus

Munday, Diane C.; Emmott, Edward; Surtees, Rebecca; Lardeau, Charles-Hugues; Wu, Weining; Duprex, W. Paul; Dove, Brian K.; Barr, John N.; Hiscox, Julian A.

Deregulation of Cell Cycle-The quantitative proteomic analysis, IPA, and subsequent validation with Western blotting revealed changes in the abundance of cell cycle regulatory complexes in HRSV-infected cells. Most notably obvious was the ablation of Cdc2 and the major cyclins responsible for cell cycle progression (Fig. 11) . Also of interest was the ablation of nucleolin (Fig. 11) , which under normal growth conditions is highly expressed in proliferating cells (97) and is responsible for correct mitosis and controlled centrosome duplication (98, 99) . The ablation of cell cycle regulatory complexes may account for the observed cell cycle arrest reported in HRSV-infected primary and A549 cells (18) and in cells infected with bovine respiratory syncytial virus (100) . A number of viruses with RNA genomes whose site of RNA synthesis is the cytoplasm have been reported to interact with the cell cycle to promote cellular conditions more favorable for viral replication. These include other negative sense RNA viruses such as measles virus, which can arrest cells in the G 0 phase to prevent an antiviral response (101) (102) (103) . Also, the positive sense RNA coronavirus infectious bronchitis virus arrests cells in G 2 /M to increase viral protein translation and progeny virus production (104) .