DEMONSTRATION OF BINDING OF DENGUE VIRUS ENVELOPE PROTEIN TO TARGET-CELLS

The nature of the initial interaction of dengue virus with target cell s and the extent to which this interaction defines tropism are unknown . Infection of some cells may involve antidengue antibody-mediated imm une adherence to cells bearing immunoglobulin Fc receptors; however, t his mechanism does not explain primary infection or the infection of c ells without Fc receptors, We hypothesized that dengue virus envelope protein mediates initial binding to target cells, To test this hypothe sis, a recombinant chimeric form of dengue type 2 virus envelope prote in was used as a probe to investigate binding to the surfaces of poten tial target cells, Envelope protein was expressed amino terminal to th e heavy-chain constant region of human immunoglobulin G containing the Fc receptor binding motif; the binding mediated by envelope determina nts was distinguishable from the binding mediated by immunoglobulin Fc determinants, We found that the recombinant chimera bound to Vero, CH O, endothelial, and glial cells through envelope protein determinants and to monocytes and U937 cells by Fc-Fc receptor interactions. The hi ghest level of binding was to Vero cells; binding was dose and time de pendent and saturable. Examination of partial-length recombinant envel ope proteins indicated that the binding motif was expressed between am ino acids 281 and 423. Recombinant envelope protein inhibited infectio n of Vero cells by dengue virus, indicating the functional significanc e of the interaction of envelope protein and target cells in infectivi ty, These results suggest that envelope protein binding to a non-Fc re ceptor could explain the cell and tissue tropism of primary dengue vir us infection.