TABLE 3.

Challenges for DENV research

Challenge
Developing an animal model of dengue disease
Understanding the role of several DENV strains and serotypes in DENV tropism in vivo
Elucidating the role of intrahost evolution of DENVs in emergence of virulent strains and the role of genetic variants and different serotypes in promoting OAS, ADE, transient autoimmunity, and unbalanced T-cell responses
Elucidating the role of DENV proteins, especially NS1 in pathogenesis
Understanding the interplay between the hemostatic and the complement systems in DENV infection
Elucidating the mechanisms by which innate immunity regulates memory B- and T-cell generation, maintenance, and activation during primary and secondary DENV infections
Elucidating the role of autoimmunity in dengue pathogenesis
Identifying serotype-specific linear and conformational B-cell epitopes and understanding their role in primary and anamnestic B-cell responses
Understanding the role of DENV immune complexes in the signaling network within target cells, especially APCs, and how it influences virus replication and priming of immune responses
Elucidating the role of the T-helper and T-cytotoxic cell repertoire, especially the private repertoire, on evolution of T-cell responses during primary and sequential heterologous DENV infections
Understanding the role of OAS in T-cell-mediated immunity in heterologous DENV infections and elucidating the factors that determine occurrence of OAS for T cells and its role in pathogenesis
Identifying soluble factors that are necessary or sufficient to induce endothelial cell dysfunction and coagulopathy seen in DHF/DSS
Identifying critical components of tight junctions and adherent junctions present in the vascular beds affected during DHF/DSS and elucidating the role that different soluble factors play in expression and functions of the several components of these junctions
Investigating the effect of demographic history of infection on the type of B- and T-cell responses elicited during primary and secondary DENV infections and on pathogenesis
Elucidating the role of host gene polymorphism, such as FcR, cytokines, chemokines, etc., in DHF/DSS pathogenesis
Understanding race- and age-dependent susceptibility to severe DENV infection