Beyond attachment: roles of DC ‐SIGN in dengue virus infection

Abstract
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 four cell types: human immature dendritic cells and NIH3T3 cells expressing either wild type DC‐SIGN or two internalization‐deficient DC‐SIGN mutants, in which either the three 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 three 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.

Graphical Table of Contents
Whether DC‐SIGN functions as merely an attachment factor for dengue virus (DENV) or whether DC‐SIGN plays further role...

Source: Traffic - January 27, 2017 Category: Research Authors: Ping Liu, Marc Ridilla, Pratik Patel, Laurie Betts, Emily Gallichotte, Lidea Shahidi, Nancy L. Thompson, Ken Jacobson Tags: ORIGINAL ARTICLE Source Type: research