Unique molecular profiling of monocyte responses to a high dose of DENV-NS1 reflected the effect of NS1 on hemostasis

Abstract

The pathogenesis of dengue is complex and requires further study. Infection with the dengue virus can lead to severe dengue, in which patients experience severe plasma leakage and excessive bleeding. The dengue virus non-structural protein 1 (DENV NS1) is among several factors that affect the outcome. The secreted form of this protein induces severe cases through direct and indirect immunopathogenesis mechanisms. Previously, we discovered that the stimulation of blood monocytes by NS1 upregulates transcripts involved in inflammation, and suppresses transcripts involved in antiviral processes. In this study, we examined the specific responses unique to high-dose NS1 exposure of cultured human monocytes. We found that genes involved in hemostasis were altered following NS1 exposure and were associated with platelet activation, fibrinolysis, and hemostatic regulation. Some of these expression changes were also observed in patients with dengue fever (DF) or dengue hemorrhagic fever (DHF). The altered expression of these genes suggests that fibrinolysis is more likely balanced during DF, whereas coagulation may be impaired in DHF.