Influenza A virus NS1 suppresses nuclear speckles promoted gene expression by inhibition of transcription.

IAV-NS1 proteins that interact with Cleavage and polyadenylation specific factor 30 are known to inhibit host gene expression. Here we report that in both transfection and infection experiments, a strong attenuation of reporter gene expression is observed when NS1 proteins are fused to protein domains guiding NS1 exclusively to nuclear speckles (NSP). NS1 proteins that are fused to domains that guide them to nuclear or non-nuclear compartments other than NSP show little or no ability to attenuate reporter gene expression. An NSP-localized NS1-effector domain is sufficient to inhibit gene expression. The protein SON is an essential component of NSP. SiRNA-mediated suppression of SON reduced the ability of NS1 to suppress the expression of a reporter gene relative to cells with fully functional NSP. Lastly, we demonstrate that the NS1-mediated suppression relies on transcriptional inhibition. Our data suggest that IAV-NS1 suppresses NSP-promoted gene expression by inhibition of transcription.