Functions of the influenza A virus NS1 protein in antiviral defense

- Influenza A NS1 protein blocks interferon (IFN) production by one or two mechanisms.
- NS1 proteins of several virus strains do not inhibit activation of IFN transcription.
- NS1 proteins of one virus strain do not inhibit 3′ end processing of IFN pre-mRNAs.
- NS1 proteins of other virus strains inhibit both steps in IFN production.

Influenza A viruses counteract host antiviral activities, especially the production of interferons (IFNs) and the activities of IFN-induced proteins that inhibit virus replication. The viral NS1 protein is largely responsible for countering these IFN antiviral responses, but there are functional differences between the NS1 proteins of different virus strains. The NS1 protein inhibits IFN production by two mechanisms: inhibition of the activation of IRF3 and IFN transcription; and inhibition of the processing of IFN pre-mRNAs. The NS1 proteins of several virus strains do not inhibit IRF3 activation, and the NS1 protein of one virus strain does not inhibit the processing of IFN pre-mRNAs. Many issues remain concerning the mechanisms of action of the various NS1 proteins in countering the IFN response.