Inhibition of IFN-beta

Inhibition of IFN-beta Since the presence of intracellular dsRNA serves as the signal for virus infection and triggers host interferon (IFN) synthesis the simplest model for viral NS1 protein function is that it sequesters dsRNA and thus prevents the downstream signaling required to activate IRF-3, NF-kB and AP-1. These findings are strongly supported by mutational analyses of NS1 that indicate that the IFN antagonist properties of NS1 depend on its ability to bind dsRNA. However, a compensatory mutation (S42G), which was acquired during the passaging of the mutant RNA-binding virus, results in partial restoration of wild-type phenotype but does not restore RNA binding. This indicates that the ability of NS1 to inhibit IFN synthesis is not solely dependent on dsRNA binding and that additional mechanisms may be involved.