Schneider J, Dauber B, Melén K, Julkunen I, Wolff T (2008): Analysis of influenza B virus NS1 protein trafficking reveals a novel interaction with nuclear speckle domains
J. Virol.: Nov 5. [Epub ahead of print].

Many proteins that function in the transcription, maturation and export of metazoan mRNAs are concentrated in nuclear speckle domains indicating this compartment to be important for gene expression. Here we show that the NS1 protein of influenza B virus (B/NS1) accumulates in nuclear speckles and causes rounding and morphological changes of these domains indicating a disturbance in their normal functions. This property was located within the N-terminal 90 amino acids of the B/NS1 protein and was shown to be independent of any other viral gene product. Within this protein domain, we identified a monopartite, importin-α binding nuclear localization signal. Reverse genetic analysis of this motif indicated that nuclear import and speckle association of the B/NS1 protein is required for the full replication capacity of the virus. In the late phase of virus infection the B/NS1 protein relocated to the cytoplasm, which occurred in a CRM1-independent manner. The interaction of the B/NS1 protein with nuclear speckles may reflect a recruitment function to promote viral gene expression. To our knowledge this is the first functional description of a speckle-associated protein that is encoded by a negative strand RNA virus.