In addition to inflammasome activation, cytoplasmic leakage of cathepsins is associated with cell death. Activation of caspase-3 is the hallmark of programmed cell death, apoptosis, and we have previously shown that caspase-3 is activated in human macrophages during influenza A virus infection [5] . To study the role of cathepsin B in influenza A virus-induced activation of apoptosis, macrophages were infected in the presence and absence of cathepsin B inhibitor, Ca-074-Me, and caspase-3 activation was analysed by Western blotting. Like caspase-1, caspase-3 is a latent zymogen, which is processed upon activation into smaller polypeptide chains: p17 and p12, which in turn form the bioactive enzyme. Influenza A virus (Udorn/72) infection clearly activated the formation of caspase-3 p17/p19 (Fig. 4D) . Furthermore, Ca-074-Me inhibited the formation caspase-3 p17/p19 in response to infuenza A viruses Udorn/72 (Fig. 4D) and Beijing 353/89 (Fig.  S3C ) confirming the role of cathepsins in the activation of apoptosis during infection. This effect was not dependent on diminished viral replication since Ca-074-Me treatment had only little effect on influenza A virus protein expression (Fig. 4D ).