Plasma Membrane DC-SIGN Clusters and Their Lateral Transport: Role in the Cellular Entry of Dengue Virus

Abstract

DC-SIGN (a single-pass transmembrane protein and C-type lectin) is a major receptor for a variety of pathogens on human dendritic cells including dengue virus (DENV), which has become a global health threat. DENV binds to cell-surface DC-SIGN and the virus/receptor complexes migrate to clathrin-coated pits where the complexes are endocytosed; during subsequent processing, the viral genome is released for replication. DC-SIGN exists on cellular plasma membranes in nanoclusters that may themselves be clustered on longer length scales that appear as microdomains in wide-field and confocal fluorescence microscopy. We have investigated the dynamic structure of these clusters using fluorescence and super-resolution imaging in addition to large-scale single particle tracking. While clusters themselves can be laterally mobile there appears to be little mobility of DC-SIGN within clusters or exchange of DC-SIGN between the clusters and the surroundings. We end this account with some outstanding issues that remain to be addressed with respect to the composition and architecture of DC-SIGN domains and some highly unusual aspects of their lateral mobility on the cell surface that may accompany and perhaps facilitate DENV infection.