The Influenza Virus NS1 Protein: Inhibitor of Innate and Adaptive Immunity

The influenza virus NS1 protein has been shown to be a multifunctional immune modulator and a virulence factor for this virus. Among its multiple functions are the inhibition of the type I interferon (IFN) system in infected cells, the binding and sequestration of dsRNA, the interference with the host mRNA processing, the facilitation of preferential viral mRNA translation, and the inhibition of dendritic cell (DC) activation. The combination of all these functions makes the NS1 protein a very potent inhibitor of immunity and allows influenza virus to efficiently escape the immune surveillance and to establish infection in the host. There are different domains in the NS1 protein that are required for specific functions, which provides several potential targets for the action of antiviral drugs. Additionally, the crystal structure of both the N-terminal RNA binding domain and the C-terminal effector domain of the NS1 protein have been resolved, potentially allowing for better antiviral drug design. Recent advances in the understanding how viruses are detected by infected cells are unveiling the mechanisms by which the NS1 protein can perform some of its multiple immune modulating activities. In this review the multiple functions of the NS1 protein are discussed and several possible options for drug targets within the influenza virus NS1 protein will be explored. Such drugs could make influenza viruses less efficient at evading the immune system in the host.