The CPSF4-binding domain of NS1 protein plays a crucial role in the alteration of p53 isoform expression and p53 transcriptional activity. A549 cells were transfected with pG13-Luc, Mdm2-Luc, Bax-Luc or p21-Luc reporter plasmids together with increasing concentrations of an NS1-expressing plasmid (either H3N2 NS1 wt or H3N2 NS1-CPSF4b mutant). p53 transactivation activity was measured after 48 h, in triplicate in two independent experiments, and expressed in relative luciferase units (RLU) compared with the empty-plasmid condition. Mean values ± standard deviations are shown, and statistical tests compared each condition with the empty-plasmid condition using one-way ANOVA and Dunnett’s posttest (*, P < 0.05; **, P < 0.01 ***, P < 0.001).