Animal models for dengue vaccine development and testing

Na, Woonsung; Yeom, Minjoo; Choi, Il-Kyu; Yook, Heejun; Song, Daesub

To understand the mechanisms of DENV infection, a more fundamental approach should be taken, by expressing human DENV receptors in mouse cells to induce infection states and establish a disease model that is effective for all DENV serotypes. Dendritic cell (DC)-specific intercellular adhesion molecule 3-grabbing non-integrin DC (SIGN) is a receptor on DC, and a significant decrease in DENV infection was observed when DCs were treated with an anti-DC-SIGN antibody [32] . In addition, it has been shown that cells that did not naturally express DC-SIGN became susceptible to DENV infection when they expressed this receptor [33] . Through polymorphic experiments using genetic modifications of the DC-SIGN promoter, it was demonstrated that the probability of developing DHF, rather than common dengue fever, is increased [34] , thus DC-SIGN should be useful for studying DHF, which is a severe symptom of DENV infection. The carbohydrate recognition domain of DC-SIGN and the E protein mannose-rich N-glycan of DENV interact to infect cells. Mannose receptor (MR), which recognizes the N-linked glycan present at N67 or N153 of the DENV E protein, is a DENV receptor on macrophages, and virus fusion was observed when this receptor was expressed on 3T3 mouse embryo fibroblasts. Similarly, when macrophages were treated with anti-MR antibodies, DENV infection was greatly decreased [35] .