Dengue virus NS1 leads to downregulation of HNF4 alpha in liver cells resulting in a decrease in coagulation factors I, V, X, and XIII, contributing to coagulopathy

Thrombocytopenia has been linked to coagulopathy of Dengue infection, and Dengue patients with coagulopathies are often administered platelet transfusion. For coagulopathies without thrombocytopenia, platelet transfusion might not help. We demonstrated the role of NS1 in coagulopathy by downregulating coagulation factors themselves. When thrombocytopenia does not exist or when thrombocytopenia as well as reduced levels of coagulation factors are the causative factors for coagulopathies, only platelet transfusion might not be effective. Alternative strategies, like administration of coagulation factor cocktails or platelet transfusion along with coagulation factor cocktail, might be promising. Our work also leads to a signaling pathway of NS1-mediated downregulation of coagulation factors via phosphorylated ERK and HNF4α. HNF4α is a transcription regulator for many other liver-based metabolic factors and pathways like lipid metabolism, carbohydrate metabolism, etc, and thus, therapeutic targeting of NS1-based downregulation of HNF4α can lead to designing therapeutic candidates for managing other Dengue-based liver dysfunction.