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

Area of Science:

• Virology
• Cell Biology
• Immunology

Background:

• Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) is a C-type lectin on dendritic cells.
• DC-SIGN binds various viruses, including dengue virus (DENV).
• Its precise role in DENV internalization remains debated.

Purpose of the Study:

• To determine if DC-SIGN is a complete receptor for DENV binding and internalization.
• To investigate the mechanism of DENV entry mediated by DC-SIGN.
• To identify potential co-receptors involved in DENV internalization.

Main Methods:

• Utilized human immature dendritic cells and NIH3T3 cells expressing wild-type or internalization-deficient DC-SIGN mutants.
• Employed confocal and super-resolution imaging.
• Applied high-content single-particle tracking to analyze DENV binding, DC-SIGN transport, and endocytosis.

Main Results:

• DC-SIGN colocalized with DENV intracellularly, ruling out plasma membrane hand-off.
• NIH3T3 cells expressing DC-SIGN, including internalization-deficient mutants, supported DENV infection.
• Internalization-deficient DC-SIGN mutants facilitated cell infection, suggesting co-receptor involvement.

Conclusions:

• DC-SIGN functions as a complete receptor for DENV binding and internalization.
• DENV internalization mediated by DC-SIGN likely involves a co-receptor.
• These findings clarify DC-SIGN's role in viral entry and host cell infection.