Dengue virus (DENV) is a major threat to military service members and global health. 5-20 of symptomaticpatients progress to severe dengue (SD), manifested by complications and sometimes death, however, there are noaccurate means to predict which patients will progress to SD. There is thus a critical need for biomarkers toeffectively predict the development of severe complications and allow adequate patient triage. The goals of thisproject are to profile the host response to natural dengue infection in multiple cell subtypes in order to identifycandidate biomarkers of dengue severity and novel targets for host-targeted anti-DENV agents; and ii) determine thefeasibility for predicting SD by our novel gene set. To achieve these goals, we have been monitoring the hostresponse to natural dengue infection in blood samples from the Colombia cohort using our novel platform andadvanced immune monitoring technologies. In parallel, we have been validating the 20-gene set predictive of SD ina larger scale and identified a more parsimonious 8-gene set with a comparable predictive power.