Interactions Between NS1 of Influenza A Viruses and Interferon-α/β: Determinants for Vaccine Development

Influenza A viruses (IAVs) cause mild to severe infections in humans with considerable socioeconomic and global health consequences. The host interferon (IFN)-α/β response, critical as the first line of defense against foreign pathogens, is induced upon detection of IAV genomic RNA in infected cells by host innate pattern recognition receptors. IFN-α/β production and subsequent activation of cell signaling result in the expression of antiviral IFN-stimulated genes whose products target various stages of the IAV life cycle to inhibit viral replication and the spread of infection and establish an antiviral state. IAVs, however, encode a multifunctional virulence factor, nonstructural protein 1 (NS1), that directly antagonizes the host IFN-α/β response to support viral replication. In this review, we highlight the mechanisms by which NS1 suppresses IFN-α/β production and subsequent cell signaling, and consider, therefore, the potential for recombinant IAVs lacking NS1 to be used as live-attenuated vaccines.