Influenza virus NS1 protein binds cellular DNA to block transcription of antiviral genes

- IAV infection activates transcription of antiviral genes.
- NS1 protein of IAV binds cellular DNA.
- NS1-dsDNA interaction prevents loading of transcriptional machinery.
- Thus, NS1 suppresses IAV-mediated transcription of antiviral genes.

Influenza NS1 protein is an important virulence factor that is capable of binding double-stranded (ds) RNA and inhibiting dsRNA-mediated host innate immune responses. Here we show that NS1 can also bind cellular dsDNA. This interaction prevents loading of transcriptional machinery to the DNA, thereby attenuating IAV-mediated expression of antiviral genes. Thus, we identified a previously undescribed strategy, by which RNA virus inhibits cellular transcription to escape antiviral response and secure its replication.