To complete our high-throughput proteomics analysis, we performed secretome characterization of influenza A virus-infected macrophages. Influenza A virus infection of human macrophages clearly induced protein secretion already at 6 h postinfection, and more robust protein secretion was seen at 9 h and 12 h time-points ( Fig. 1C , Table S1 ). Our data shows that influenza A virus infection of macrophages activates both conventional as well as unconventional protein secretion [19] . Examples of the conventionally secreted proteins include e.g. C-C motif chemokine 3, C-C motif chemokine 24, complement C1q subcomponent subunit B, epididymal secretory protein E1, macrophage colony-stimulating factor 1, macrophage metalloelastase, matrix metalloproteinase-9, metalloproteinase inhibitor 2, and plasminogen activator inhibitor 1. The unconventionally secreted proteins include several danger-associated molecular pattern molecules (DAMPs) like amyloid beta A4 protein, annexins, galectins, heat shock proteins, high-mobility group box proteins (HMGBs), and S100 proteins (Table 1) . Enhanced secretion of amyloid beta A4 protein, galectin-3, HMGB1, and S100-A9 protein in response to influenza A virus infection was verified by Western blotting (Fig. S1D ). In addition to DAMPs, secretion of several other proteins known to be secreted through unconventional secretory pathway was enhanced. These include cystatins A and B, macrophage migration inhibitory factor, and thioredoxin. Interestingly, influenza A virus infection of macrophages also activated the secretion of Ras-related proteins Rab- 1A, Rab-2b, Rab-10, and Rab11, as well as several components of vacuolar ATPases (Table 1) . Furthermore, enhanced secretion of several lysosomal proteases, cathepsins, was seen in cell culture supernatants of influenza A virus-infected macrophages.