Dengue virus infection: current concepts in immune mechanisms and lessons from murine models

Dengue viruses (DENV), a group of four serologically distinct but related flaviviruses, are responsible for one of the most important emerging viral diseases. This mosquito-borne disease has a great impact in tropical and subtropical areas of the world in terms of illness, mortality, and economic costs, mainly due to the lack of approved vaccine or antiviral drugs. Infections with one of the four serotypes of DENV (DENV-1-4) result in symptoms ranging from an acute, self-limiting febrile illness (dengue fever, DF) to severe dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). We reviewed the existing mouse models of infection, including the DENV-2 adapted strain P23085. The role of CC chemokines, IL-17, IL-22 and invariant NKT (iNKT) cells in mediating the exacerbation of disease in immune competent mice is highlighted. Investigations in both immune deficient and competent mouse models of DENV infection may help identify key host-pathogen factors and devise novel therapies to restrain the systemic and local inflammatory responses associated to severe dengue infection