IAV NS1

The non-structural protein (NS1) of influenza A virus is a 26kD protein. It prevents polyadenylation of cellular mRNAs to circumvent antiviral responses of the host. NS1 also inhibit splicing of pre-mRNA by binding to a stem-bulge region in U6 small nuclear RNA (snRNA). Via binding to dsRNA, the NS1 protein blocks the activation of the dsRNA-activated protein kinase(PKR) in vitro. This kinase phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (elF-2 alpha), leading to a decrease in the rate of initiation of translation. In the absence of NS1, this pathway is inhibited during anti-viral response to halt all protein translation – thus stopping the synthesis of viral proteins; however, the influenza virus' NS1 protein is an agent that circumvents host defenses to allow viral gene transcription to occur. The NS1 protein can be divided into an N terminal (RNA binding) domain and C terminal (effector domain) and some mutations and deletions in NS1 may serve as the virulence marker for influenza variants.