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

Warnking K., Klemm C., Löffler B., Niemann S., van Krüchten A., Peters G., Ludwig S., Ehrhardt C.

Abstract

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.