Zika virus non-structural protein 1 (NS1) (NS1)

The Zika virus non-structural protein 1 (NS1) is a ~48-50 kDa glycoprotein essential for the flavivirus lifecycle, functioning primarily in the endoplasmic reticulum (ER) lumen where it exists as a homodimer. NS1 remodels ER membranes by inserting hydrophobic regions, such as the N-terminal β-roll and flexible loops, into the inner leaflet to induce perinuclear aggregation and form convoluted networks resembling viral replication compartments, which are critical for RNA synthesis and viral amplification. This membrane-binding and curvature-altering activity depends on specific motifs like the greasy finger and wing domains, enabling NS1 to create invaginations without direct contact with cytoplasmic replication machinery. Secreted as a hexameric lipoprotein, NS1 modulates host immune responses, interacts with glycoproteins like prM and E for virion production, and contributes to pathogenesis by evading innate immunity. Crystal structures (e.g., PDB 5K6K) reveal an elongated hydrophobic surface for membrane association and a variable polar outer face with glycosylation sites, distinguishing Zika NS1 from homologs like dengue NS1 in insertion depth and cholesterol affinity. As a validated therapeutic target, inhibiting NS1's ER remodeling or secretion could block Zika replication, though no approved drugs exist.

Other names

Zika NS1ZIKV NS1