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.

STAT1 and ISG15 were identified as being more abundant in HRSV-infected cells when compared with mock-infected cells (Fig. 5) . Both of these observations were consistent with previous observations using HRSV-infected cells and in vivo models (20, 45, 79) . In the pathway analysis, STAT1 was linked to IFN ␣/␤ (Fig. 5) . STAT1 activity is also regulated by phosphorylation, and HRSV uses distinct mechanisms to either impair STAT1 phosphorylation or increase phosphorylation of STAT1␤ (a STAT1 variant) to repress IFN expression (80) . HRSV proteins NS1 and NS2 strongly inhibit IFN ␣/␤ by preventing the phosphorylation of the IFN regulatory factor-3 (15, 16) . However, the molecular pathology of HRSV infection and the mechanisms by which it circumvents IFN are still not fully understood. Different strains of HRSV can differ in their ability to block IFN type I synthesis, and likewise, cell line choice is important in such pathway studies. Therefore, a comparison of different HRSV strains using differential isotopic labeling and different cell lines (e.g. macrophages) may prove useful in further characterizing HRSV infection.