Ns1 dating in usa org
In contrast, the NS1 proteins of other influenza virus strains, including A/Victoria/3/75 (Vic), efficiently limit ISRE activation probably by blocking a posttranscriptional process (10).
These data suggest that, unlike other NS1 proteins, PR8/NS1 is incapable of inhibiting the posttranscriptional processing of cellular pre-m RNAs, and thus may limit the synthesis of IFN-β by a pretranscriptional mechanism that is distinct from the posttranscriptional process adopted by many other strains.
These data suggest that activation of PI3K signaling in influenza A virus-infected cells is important for efficient virus replication.
Influenza A viruses are globally important human and animal respiratory pathogens that are responsible for both seasonal “flu” outbreaks, and periodic world-wide pandemics (1).
We observed that activation of PI3K also aids the replication of influenza A virus.
By using reverse genetics, a mutant influenza virus (Ud strain) was generated that contains an amino acid substitution in NS1 at the highly conserved tyrosine residue 89.
Here, we report that NS1 binds directly to p85β, a regulatory subunit of phosphatidylinositol-3-kinase (PI3K), but not to the related p85α subunit.
This mutant is unable to bind p85β or activate PI3K signaling, and forms smaller plaques and grows less efficiently than WT Ud influenza virus.
A HEp2 cell line was isolated that constitutively expresses a V5 epitope-tagged form of PR8/NS1, an influenza virus protein that has been reported to limit both the production and downstream effects of IFN (3, 4).
Mutational analysis of a potential SH2-binding motif within NS1 indicated that the highly conserved tyrosine at residue 89 is important for both the interaction with p85β, and the activation of PI3K.
A mutant influenza virus (A/Udorn/72) expressing NS1 with the Y89F amino acid substitution exhibited a small-plaque phenotype, and grew more slowly in tissue culture than WT virus.