Development of a novel mouse model for dengue virus infection.

In the present study, we established an animal model for dengue virus infection using severe combined immunodeficient mice transplanted with a human hepatocarcinoma cell line (HepG2). At 7-8 weeks after transplantation, the HepG2-grafted mice were infected intraperitoneally with dengue virus type 2 (DEN-2). A higher titer of the virus was detected in the liver and serum but not in the brain in the early stage of postinfection. When the mice showed paralysis, the highest titer of virus was detected in the serum and brain. DEN-2 antigens were also found in HepG2 cells of the liver in the early stage and some neurons of the brain in the late stage. Upon clinical examination, thrombocytopenia, prolonged partial thromboplastin time, and increased hematocrit, blood urea nitrogen, and tumor necrosis factor alpha were seen in the paralyzed mice. Moreover, mild hemorrhage in the liver and tarry stool in the small intestine were observed in some mice. Our results show some similarities to human DEN infection and this mouse model might be valuable for studying some aspects of pathogenesis of this disease.