Lastly, rSARS-CoV-2N4A infection of A549-ACE2 cells led to a higher induction of a canonical ISG, MX1, than infection with rSARS-CoV-2WT (Fig. 6F); this observation could be a result of altering the viral gene ORF9B that overlaps with N. In summary, we found that ablation of the phosphorylation of N-terminal N residues inhibited viral production, albeit less significantly than genetic inhibition of p38β, suggesting that p38 impacts viral replication by modulating both viral and host substrates. The gene discussed is ACE2; the disease is infection.