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Potential pathogenic roles of dengue nonstructural protein 1 (NS1) and its antibodies in dengue virus infection

NS1 is involved in DENV replication within cells. The NS1 dimer can be anchored at the cell membrane or secreted out.
NS1 can bind to C4 protein and promotes its degradation.
NS1 can bind to prothrombin and inhibit its activation.
The binding of NS1 to cells may enhance endocytosis and cytokine production, which may increase vascular permeability. In the right panel,
anti-NS1 antibodies that cross-react with endothelial cells may induce endothelial damage.
Anti-platelet antibodies elicited by NS1 may inhibit platelet aggregation and cause thrombocytopenia. It is the integrated effects of NS1 and its antibodies, and the immunocomplexes they formed that may contribute to the development of thrombocytopenia, vascular leakage, and coagulopathy during the critical phase of DHF/DSS.

Macrophage migration inhibitory factor (MIF)-induced autophagy plays important role to cause vascular leakage during infection

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