Hematological Changes and Immunopathology in Whole Blood Infection with Dengue Virus

Dengue virus (DENV) infection risks severe systemic immune reactions in patients. The condition is marked by thrombocytopenia, macrophage activation syndrome, and hemophagocytosis in severe complications. To simulate acute infection and investigate the undefined mechanisms of DENV's capacity to induce cytopathic effect and underlying the progression of thrombocytopenia, we demonstrated ex vivo whole blood DENV infection. After a single day of infection, whole blood cultures contain viral non-structural protein 1 (NS1) but no further viral replication. Significant vacuolization and thrombophagocytosis phenomenon was seen after DENV infection. Numerous changes were found in the immunological profile, including a significant decrease in CD14+ monocytes and CD11c+ dendritic cells and decreased platelet count in the DENV infection model. In addition, we discovered abnormal TNF-α production strongly associated with vacuolization and thrombophagocytosis in the DENV-inoculation groups. Neutralizing TNF-α considerably rescued DENV-induced such effects. This study showed that an increase in TNF-α titers is accompanied by cellular vacuolization and thrombophagocytosis followed by thrombocytopenia
Keywords
TNF-α, vacuolization, thrombophagocytosis, dengue infection, ex vivo