During budding from the plasma membrane, influenza A viruses (IAVs) incorporate host proteins, but the role of these proteins in the viral life cycle is poorly understood. Berri et al. now show that the membrane protein annexin V (A5), which is upregulated during IAV infection and is incorporated into viral particles, enables escape from immune detection. The authors found that A5 incorporation inhibited interferon-γ (IFNγ)-mediated STAT1 phosphorylation and the subsequent production of CXC-chemokine ligand 10 (CXCL10) in infected macrophages, whereas knockdown of A5 using a small interfering RNA restored IFNγ signalling and decreased viral replication in macrophages and in the lungs of mice. These findings demonstrate that IAV has evolved a strategy to exploit host proteins for the subversion of immunosurveillance.