Models of dengue virus infection

Abstract

The need for models of dengue disease has reached a pinnacle as the transmission of this mosquito-borne virus has increased dramatically. Little is known about the mechanisms that lead to dengue fever and its more severe form, dengue hemorrhagic fever; this is owing to the fact that only humans show signs of disease. In the past 5 years, research has better identified the initial target cells of infection, and this has led to the development of models of infection in primary human cell cultures. Mouse-human chimeras, containing these target cells, have also led to progress in developing animal models. These advances should soon end the stalemate in testing antivirals and vaccine preparations that had necessarily been done in incomplete or irrelevant models.

Figure 1

Reconstitution of NOD/SCID mice with human hematopoietic progenitor cells. Irradiated NOD/SCID mice are injected with CD34+ cells purified from human umbilical cord blood. Six to 8 weeks later reconstitution levels of human CD45+ cells (panleukocyte marker) and CD11c+/CD123+ cells (DC marker) are determined by flow cytometry. Details are provided in Refs [41,42].

Figure 2

Levels of human cells in reconstituted NOD/SCID mice. NOD/SCID mice reconstituted with CD34+ cells develop functional subsets of human dendritic cells in a variety of tissues. They have high percentages of human plasmacytoid dendritic cells (pDCs) and myeloid dendritic cells (mDCs) in bone marrow, spleen and blood. Immature Langerhans cells can be detected in the skin. Details are provided in Refs [41,42].