Influenza non-structural protein 1 (NS1 protein)

Influenza non-structural protein 1 (NS1 protein) is a multifunctional immunomodulatory protein encoded by all strains of influenza A virus[1][5][7]. It is a ~26 kDa protein composed of two major domains: an N-terminal RNA-binding domain (RBD; residues 1–73) and a C-terminal effector domain (ED; residues 88–202), linked by a flexible interdomain region (LR); the C-terminal tail (CTT) is intrinsically disordered[7]. NS1 antagonizes key host defense responses, mainly by suppressing interferon signaling and blocking host gene expression: it inhibits polyadenylation and splicing of cellular mRNAs, inhibits nuclear export of host mRNA by interacting with nuclear RNA export factors (NXF1-NXT1) and CPSF30, and binds double-stranded RNA and proteins involved in antiviral responses such as RIG-I[1][3][5][7]. NS1’s high conformational plasticity enables it to interact with diverse host factors and explains its strain-dependent regulatory functions[2][4][6][9]. It plays a central role in influenza viral replication, pathogenesis, and virulence, making it a validated antiviral target in research, though it is not yet the basis of any clinically approved drugs. Therapeutic targeting is challenging due to strain diversity and its multiple cellular interactions[5][7][9].

Other names

NS1influenza A virus NS1 proteinnon-structural protein 1

Inhibition of interferon signaling; Antagonism of RIG-I dependent pathway; Suppression of host mRNA processing and export; Inhibition of host antiviral defenses[1][3][7]