Analysis of Saturation Binding and Saturation Infection for Dengue Serotypes 1 and 2 in Liver Cells

Abstract

Objective: The liver has been increasingly recognized as a significant target organ in the pathogenesis of dengue virus infection. However, only two contradictory studies have examined the binding of the dengue virus to liver cells. This study therefore sought to investigate the binding of the dengue virus to HepG2 cells. Methods: Radiolabeled dengue virus serotypes 1 and 2 were prepared through viral propagation in Vero cells. Increasing amounts of virus were then incubated with HepG2 cells to determine the ability of the virus to achieve saturation of binding on HepG2 cells. Results: Results indicated that it was not possible to reach saturation of binding under experimentally achievable conditions. We then sought to determine whether it was possible to reach a state of saturation of infection, by using increasingly high titers of virus on a constant number of cells. Dengue serotype 1 showed no evidence of saturation of infection, even at titers of 5,000 viruses per cell. In contrast, dengue serotype 2 became saturated at levels of approximately 3,000 viruses per cell. Conclusions: These results are consistent with proposals that dengue virus binding to cells is mediated initially through a low-affinity interaction with an abundant molecule on the surface of the cell and secondly through interaction with a less commonly expressed molecule, which is required for viral internalization.