Super‐infection with Staphylococcus aureus inhibits influenza virus‐induced type I IFN signalling through impaired STAT1‐STAT2 dimerization

Summary Bacterial super‐infections are a major complication in influenza virus‐infected patients. In response to infection with influenza viruses and bacteria, a complex interplay of cellular signalling mechanisms is initiated, regulating the anti‐pathogen response but also pathogen‐supportive functions. Here, we show that influenza viruses replicate to a higher efficiency in cells co‐infected with Staphylococcus aureus (S. aureus). While cells initially respond with increased induction of interferon beta upon super‐infection, subsequent interferon signalling and interferon‐stimulated gene expression are rather impaired due to a block of STAT1‐STAT2 dimerization. Thus, S. aureus interrupts the first line of defence against influenza viruses, resulting in a boost of viral replication, which may lead to enhanced viral pathogenicity. Influenza A viruses and Staphylococcus aureus are major causative agents of severe respiratory diseases. Bacterial super‐infections represent the prime complication of severe influenza. In this study we demonstrate that Staphyloccous aureus inhibits STAT1 phosphorylation and subsequently STAT1‐STAT2 dimerization, which leads to a reduced antiviral defence state of the cell, resulting in increased viral replication. This newly identified mechanism may promote enhanced pathogenicity during bacterial super‐infection.