Beyond attachment: Roles of DC‐SIGN in dengue virus infection. (28th February 2017)

• Record Type: Journal Article
• Authors: Liu, Ping; Ridilla, Marc; Patel, Pratik; Betts, Laurie; Gallichotte, Emily; Shahidi, Lidea; Thompson, Nancy L.; Jacobson, Ken
• Is Part Of: Traffic. Volume 18:Number 4(2017)
• Page Start: 218
• Page End: 231
• Publication Date: 2017-02-28
• Subjects: 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; Biological transport -- Periodicals; 571.6
• DOI: 10.1111/tra.12469
• Languages: English
• ISSNs: 1398-9219

Abstract

Abstract : 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. Abstract : Whether dendritic cell‐specific intercellular adhesion molecule‐3‐grabbing non‐integrin (DC‐SIGN) functions as merely an attachment factor for dengue virus (DENV) or whether DC‐SIGN plays further roles beyond attachment has been controversial. We use mammalian cell culture models, as well as primary dendritic cells, and high resolution, quantitative fluorescence microscopy to track the movements of DC‐SIGN and DENV during viral entry. Our results support a model in which DC‐SIGN captures DENV and participates, along with a co‐receptor, in DENV internalization via clathrin‐coated structures and subsequent trafficking to early endosomes.