Nonstructural Protein |
NS1 Protein |
Description |
NS1 is the first non-structural protein in the Dengue polyprotein, following Envelope protein and preceding the NS2A protein. It is a 46 kD glycoprotein, with two glycosylated asparagines, and 12 cysteines that form 6 disulfide bridges. During translation NS1 is translocated into the lumen of the ER where it dimerizes and stays membrane associated although it does not contain a hydrophobic membrane spanning region. The protein is found inside intracellular organelles that are enriched in other viral proteins and double stranded RNA corroborating evidence that NS1 is essential for viral replication by an unknown mechanism.
Additionally, NS1 is exported through the Golgi excretory pathway and appears on the outside plasma membrane of infected cells, anchored into the membrane by a glycosyl-phosphatidylinositol (GPI) linked to the NS1 protein. It has been suggested that in a Dengue patient antibodies against NS1 may bind to the NS1 protein on the cell surface and activate GPI-mediated signaling in the infected cell possibly enhancing viral replication or disease pathology [Jacobs et al. (2000)]. |
Function |
Unknown.
Suggested to play a role in viral RNA replication which is supported by findings from experiments on NS1 from Yellow Fever |
Cellular Location |
Cryo-EM studies have shown that Dengue NS1 is found associated with virus-containing vesicles in mammalian cells and large virus-induced vacuoles in mosquito cells [Mackenzie et al. (1996)]. Immunofluorescent double labeling studies showed that NS1 localizes in perinuclear and cytoplasmic foci [Westaway and Goodman (1987)] that only partially overlap with the distribution of Dengue E-protein. Cytoplasmic NS1 overlaps almost completely with double stranded RNA [Mackenzie et al. (1996)]. NS1 is also found on the cell membrane [Stohlman et al. (1975), Westaway and Goodman (1987)], anchored into the membrane by a glycosyl-phosphatidylinositol group attached to the NS1 protein [Jacobs et al. (2000)]. |
Structure |
No crystal structure is known. |
Synonyms |
NS-1, nonstructural protein 1, NV-3, SCF |
References (Pubmed)
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10698995 , 11825945 , 14981082 , 10233920 , 8659120 , 8985349 , 10364366 , 827377 , 15878791 , 1165590 , 3034209 , 10928995 , 8389081 , 8176380 |