Beyond attachment: Roles of DC-SIGN in dengue virus infection

作者：Liu Ping; Ridilla Marc; Patel Pratik; Betts Laurie; Gallichotte Emily; Shahidi Lidea; Thompson Nancy L; Jacobson Ken^*

来源：Traffic, 2017, 18(4): 218-231.

DOI：10.1111/tra.12469

• antigen-presenting cells
• C-type lectin receptor
• DC-SIGN
• dengue virus
• fluorescence microscopy
• in vivo trafficking
• quantitative colocalization
• super-resolution imaging
• viral entry
• viral receptor

Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), a C-type lectin expressed on the plasma membrane by human immature dendritic cells, is a receptor for numerous viruses including Ebola, SARS and dengue. A controversial question has been whether DC-SIGN functions as a complete receptor for both binding and internalization of dengue virus (DENV) or whether it is solely a cell surface attachment factor, requiring either hand-off to another receptor or a co-receptor for internalization. To examine this question, we used 4 cell types: human immature dendritic cells and NIH3T3 cells expressing either wild-type DC-SIGN or 2 internalization-deficient DC-SIGN mutants, in which either the 3 cytoplasmic internalization motifs are silenced by alanine substitutions or the cytoplasmic region is truncated. Using confocal and super-resolution imaging and high content single particle tracking, we investigated DENV binding, DC-SIGN surface transport, endocytosis, as well as cell infectivity. DC-SIGN was found colocalized with DENV inside cells suggesting hand-off at the plasma membrane to another receptor did not occur. Moreover, all 3 DC-SIGN molecules on NIH3T3 cells supported cell infection. These results imply the involvement of a co-receptor because cells expressing the internalization-deficient mutants could still be infected.

• 出版日期2017-4